Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 2nd International Conference on Pharmaceutical Chemistry Barcelona, Spain.

Day 1 :

Keynote Forum

Vakhtang Barbakadze

Tbilisi State Medical University, Georgia

Keynote: Caffeic Acid-Derived Biopolyether from Medicinal Plants as Anticancer Agent
Pharmaceutical Chemistry 2017 International Conference Keynote Speaker Vakhtang Barbakadze photo
Biography:

Vakhtang Barbakadze has completed his Ph.D and D.Sci. at the ages of 33 and 54 years from Zelinsky Instiute of Organic Chemistry, Moscow, Russia and Durmishidze Institute of Biochemistry and Biotechnology, Tbilisi, Georgia, respectively. He is the head of Department of Plant Biopolymers and Natural Products Chemical Modification at the Tbilisi State Medical University I.Kutateladze Institute of Pharmacochemistry. 1996 and 2002 he has been a visiting scientist at Utrecht University (faculty of pharmacy), The Netherlands, by University Scholarship and The Netherlands organization for scientific research (NWO) Scholarship Scientific Program, respectively. He has published more than 83 papers in reputed journals.

Abstract:

A new series of  linear and regular caffeic acid-derived polyether, namely poly[3-(3,4-dihydroxyphenyl)glyceric acid] (PDPGA) was isolated and identified in the water-soluble, high molecular  weight fractions obtained  from  Symphytum asperum, S.caucasicum, S.officinale, S.grandiflorum and  Anchusa italica (Boraginaceae). According to data of 13C, 1H NMR, 2D 1H/13C HSQC experiment the polyoxyethylene chain is the backbone of the  polymer  molecule.  The 3,4-dihydroxyphenyl  and  carboxyl  groups are  regular  substituents  at  two  carbon  atoms  in the chain. The repeating unit of this polymer is 3-(3,4-dihydroxyphenyl)glyceric acid  residue. Most of the carboxylic groups of PDPGA from A. italica and S.grandiflorum unlike the polymer of  S.asperum, S.caucasicum and S.officinale are methylated. The 2D DOSY experiment gave the similar diffusion coefficient for the methylated and non-methylated signals of A. italica PDPGA. Both sets of signals fell in the same horizontal. This would imply a similar molecular weight for methylated and non-methylated polymers. The synthesis of racemic monomer of PDPGA was carried out via asymmetric dihydroxylation  of  trans-caffeic acid derivatives using a potassium osmate catalyst and cinchona  alkaloid  derivatives  as chiral auxiliaries. PDPGA and monomer  exerted  anti-cancer efficacy  in vitro  and  in vivo  against    human  prostate cancer (PCA) cells  via  targeting  androgen  receptor,  cell  cycle  arrest  and  apoptosis  without  any  toxicity, together  with  a strong  decrease  in  prostate  specific antigen  level in plasma. However, our results showed that anticancer efficacy of  PDPGA is more effective compared to its synthetic  monomer. Overall, this study identifies PDPGA as a potent agent against PCA without any toxicity, and supports  its clinical application.

Pharmaceutical Chemistry 2017 International Conference Keynote Speaker Afzal R Mohammed photo
Biography:

Professor Afzal Mohammed holds a personal Chair in Pharmaceutics and has research expertise in paediatric medicines development which includes pharmaceutical excipient characterization, process and technology innovation to develop orally disintegrating tablets.  He has over 15 years of experience in developing novel pharmaceutical processes and formulations and is the lead inventor for dry particle coater. He has over 100 publications including research articles, review papers, book chapters and patent applications.  

Abstract:

Dry powder coating is a micro particle engineering process and involves the adsorption of “guest” particles onto the surface of “carrier” particles. This process requires conditions that enable frequent contact between guest and carrier particles, particle adsorption, and ultimately lowering of surface energy of the binary mixture. Although the theoretical paradigm for dry-coating is known, progress and pragmatic translation have been limited owing to the lack of processes and devices capable of producing composite particles while maintaining the innate characteristics of both components (guest and carrier). For instance, mechanofusion works on the principle of high centrifugal forces that generate heat thereby limiting its pharmaceutical application to heat labile materials.  Similarly, processing materials using hybridiser can lead to particle attrition. One of the distinct advantages of this technology is the cross application of the fundamental principles to develop solutions for a wide range of different problems. For instance understanding the role of surface texture of carrier particles on the strength of interaction between the guest and carrier particles can provide vital information on its impact on flowability, guest stability (as a composite particle) as well as functionality of the resultant particles. Research at Aston University within our group has led to the development of a dry particle coater which can produce micro functionalised particles. We have characterised the resultant particles using range of techniques including AFM, surface interferometry, confocal microscopy, inverse gas chromatography and particle size analysis. The resultant particles were studied for flowability enhancement, content uniformity and micro particle based modified drug release.

Keynote Forum

Rongshi Li

University of Nebraska Medical Center, USA

Keynote: Fragment-based, Structure-guided and Natural Product-derived Small Molecules as Antibiotic and Anticancer Agents

Time : 9:50- 10:15

Pharmaceutical Chemistry 2017 International Conference Keynote Speaker Rongshi Li photo
Biography:

Abstract:

Natural products, their derivatives, metabolites, and mimics account for approximately half of the New Chemical Entities for drug discovery. To date, natural products have provided the largest supply of successful drug leads [Newman and Cragg, J. Nat. Prod. 2012, 75, 311]. Marine natural products have contributed to eight drugs or cosmeceuticals that were approved by the US Food and Drug Administration and European Medicines Agency [Li, R. Med. Res. Rev. 2016, 36, 3 and 169]. Fragment-based and structure-guided drug design and discovery are powerful tools. Coupling these tools with natural product-derived fragments and scaffolds will expedite successful outcomes in drug discovery and development. This presentation will discuss the design, synthesis, and Structure- Activity-Relationships of natural product fragments and their derivatives for their development as potential antibiotic and anti-cancer agents.
Acknowledgment: This work is partially supported by R01CA173056 (NIH/NCI, PI: Li), Nebraska Research Initiative (NRI) grant (State of Nebraska, PI: Li), Pediatric Cancer Research Program LB905 (State of Nebraska, PI: Coulter) and startup funds (University of Nebraska Medical Center,
PI: Li).

Pharmaceutical Chemistry 2017 International Conference Keynote Speaker Catherine GUILLOU photo
Biography:

Research activities developed within Catherine Guillou’s group are centred on the development of new methodologies, their application to the total synthesis of biologically active natural products and the design of enzyme inhibitors involved in cancer and Alzheimer’s disease. She is co-authors of 58 publications and 8 patents.

Abstract:

Kinesins constitute a superfamily of microtubule-based motor proteins with important cellular functions ranging from intracellular transport to cell division. Some kinesin family members function during the mitotic phase of the eukaryotic cell cycle and are crucial for the successful progression of cell division. MKLP-2 (also known as Kif20A, RabK6, RB6K, Rab6KIFL, Rabkinesin6) a member of the kinesin-6 family plays an essential role during cytokinesis and is overexpressed in various cancers such as pancreatic cancer, bladder cancer, breast cancer, small-cell lung cancer, hepatocarcinogenesis, melanoma and gastric cancer. Furthermore, MKLP-2 is weakly detectable or absent in the normal spleen, lymph nodes, pancreas, lung, brain, liver, kidney and skeletal muscle. MKLP2 is involved in the relocation of chromosome passenger complex CPC (which consists of Aurora B, INCENP, surviving and borealin) to the spindle midzone. Down regulation of MKLP2 inhibits the growth of gastric and pancreatic cancer cells. We recently identified one compound (named paprotrain) as the first known inhibitor of MKLP-2. Paprotrain does not inhibit others members of the kinesin superfamily involved in mitosis. The synthesis, the structure-activity relationships and the biological activities will be discussed.

  • Featured Speakers

Chair

Speaker Slots are Available for Day 1

Session Introduction

Mark McLaughlin

Merck Sharp & Dohme (MSD) Dept. of Process Research and Development, USA

Title: Mutagenic Impurities in Pharmaceuticals: ICH M7, Purge Factors and the Mirabilis Project
Speaker
Biography:

Dr. Mark McLaughlin received his Ph.D from Strathclyde University under the joint supervision of Prof. Kerr and Prof. Pauson. He completed two post-doctoral appointments at the University of California, Berkeley with Prof. Rapoport and Prof. Heathcock. He received further education at the ETH, Switzerland (Prof. Diederich) and additional industrial experience at GSK (medicinal chemistry) and Astrazeneca (process chemistry). He joined MSD in 2003 as a Senior Research chemist and is currently a Principal Scientist. In addition to project leader responsibilities for the development of novel chemical processes supporting new drug applications, Mark has served as a “subject matter expert” within the Process Chemistry Dept. at MSD on the topic of mutagenic impurities. Contact: [email protected]; Merck Research Labs PO Box 2000, RY800-C269 Rahway, NJ 07065.

Abstract:

Mutagenic impurities (MIs) are a special category of impurities that can be present in active pharmaceutical ingredients (APIs). The understanding, detection, and control of MIs have received increasing industry and regulatory attention over the past decade. Originated by Teasdale in 2010,1,2 the concept of “purge factor calculation” as a means to understand the fate of MIs in synthetic processes has been validated by various independent groups, including its application to a development project at MSD that was described in a recent publication.3 This approach can reduce the burden of analytical testing for MIs without compromising patient safety, provided a scientifically rigorous approach is taken, backed up by sufficient theoretical and/or analytical data. Moreover, specific reference to this method is provided in the accepted regulatory guidance – ICH M7 Option 4 - which was released in 2014. This presentation provides some background to the concept of purge factor calculation and introduces a consortium-led initiative, the Lhasa Mirabilis Project.4  The Mirabilis consortium seeks to develop an industry-standardised approach, providing an expert and scientifically robust software for the automated calculation of purge factors for potentially mutagenic impurities in a synthetic route. 

Francisco Alonso

Universidad de Alicante, Spain

Title: Copper nanoparticles in organic synthesis
Speaker
Biography:

Francisco Alonso received his B.Sc. (1986), M.Sc. (1988), and Ph.D. (1991) degrees in Chemistry from the University of Alicante (Spain). After a postdoctoral stay (1992–1994) at the University of Oxford (UK) with Prof. S. G. Davies, he moved back to the University of Alicante, where he is Full Professor of Organic Chemistry, Director of the Instituto de Síntesis Orgánica (ISO) and coordinator of the doctorate programme “Organic Synthesis”. He has authored 115 manuscripts, 3 patents and several book chapters, being co-founder of Medalchemy S. L. His research is focused on the development of new synthetic methodologies involving transition-metal nanoparticles and on the synthesis of biologically active natural or synthetic molecules. He is a member of the advisory board of Current Green Chemistry.

Abstract:

Some years ago, we developed a catalyst consisting of copper nanoparticles on activated carbon (CuNPs/C) which was shown to be very versatile in the synthesis of 1,2,3-triazoles through click chemistry.1 More recently, we have effectively accomplished the multicomponent synthesis of indolizines using 0.5 mol% CuNPs/C as catalyst in dichloromethane.2 Interestingly, the same procedure, when applied in the absence of solvent using piperidine as the secondary amine, has led to heterocyclic chalcones with exclusive Z stereochemistry. The aforementioned copper-catalyzed three-component synthesis of indolizines, when followed by heterogeneous catalytic hydrogenation, allowed the straightforward preparation 1-dialkylamino-3-substituted indolizidines with high chemo- and diastereoselectivity, though an overall atom-economy protocol.Copper nanoparticles on zeolite Y has been found to be an effective catalyst for the cross-dehydrogenative coupling of tertiary amines and terminal alkynes (producing propargylamines) in the presence of tert-butyl hydroperoxide as the oxidant, without the need of an inert atmosphere and in the absence of solvent, using 1.5 mol% catalyst.4 The catalyst is reusable and more efficient than an array of commercial catalysts. All types of compounds presented, 1,2,3-triazoles, indolizines, chalcones, indolizidines and propargylamines, are of pharmacological interest, some of which have shown in-vitro prominent activity.

Speaker
Biography:

Feng ZHANG has completed his PhD at the age of 26 years from Second Military Medical University, and has served as an assistant Professor in Clinical Pharmacy for Drug Safety and Effectiveness since her graduation. For chemical drugs, she promotes better standardization of analytical practices in LC-MS based therapeutic drug monitoring analyses in clinical application. She has published more than 11 SCI papers as (co)first author, and is responsible for four funds as a project leader. She also has applied for 4 Chinese patents. 

Abstract:

Multiple myeloma (MM), a malignant neoplastic serum-cell disorder, has been a serious threat to human health. Determination of 6 commonly used drug concentrations, including thalidomide (THD), lenalidomide (LND), cyclophosphamide (CTX), bortezomib (BTZ), dexamethasone (DXM) and adriamycin (ADM), in MM patients was of great clinical interest. Drug pharmacokinetic monitoring was important to ensure safety and efficacy during chemotherapy. We reported a method for the rapid and simultaneous measurement of the above therapeutics by liquid chromatography-tandem mass spectroscopy (LC–MS/MS) method with solid phase extraction. Analysis was performed on a Waters XBridge®BEH C18 column (2.5 μm, 2.1mm × 50 mm), with formic acid aqueous solution and acetonitrile as the mobile phase at flow rate 0.3 mL/min. All analytes showed good correlation coefficients (r > 0.996), and LLOQ of THD, LND, CTX, BTZ, DXM and ADM were 4, 2, 2, 2, 2 and 2 ng/mL, respectively. The inter- and intra-day precisions and stability were expressed as variation coefficients within 15% and relative error less than 15%. Dilution effect, carryover and incurred sample reanalysis were in the acceptable levels. Method validation was investigated according to the 2015 edition Chinese Pharmacopoeia guidelines, as US FDA (2013, revision 1) required. The descried method was successfully applied to determine the clinical incurred serum samples from MM patients, and the tested results were also provided to the doctors for consideration. The LC–MS/MS based assay may improve future clinical studies evaluating common therapeutics for MM treatment

Speaker
Biography:

Gervais Bérubé completed his Ph.D. in 1986 in the field of Organic Chemistry at the Université de Sherbrooke. After completing three post-doctoral stays initially in the field of Organic Chemistry, then in Oncology and lastly in Immunology, he became assistant professor of Medicinal Chemistry in the School of Pharmacy, Memorial University of Newfoundland. He is now professor of Organic Chemistry at the Université du Québec à Trois-Rivières. His main research interest is the design and development of new anticancer drugs. He has published more than 76 papers in reputed journals and presented more than 110 communications in diverse meetings.

Abstract:

The discovery of new molecules possessing multiple biological properties in a single entity is a subject of great interest to the scientific community. A simple compound previously used in our laboratory as a heterobifunctional linker to construct immunoconjugates was identified as a potential lead drug showing anti-inflammatory, anti-metastatic as well as anticancer activities. The lead compound is made in only three chemical steps from para-aminobenzoic acid with 43% overall yield. Its structure can be modified to give alternative analogs with similar activities. The prospect of lead optimization is significant. This communication will highlight the chemical and biological potential (in vitro and in vivo) of these type of molecules tested on bladder cancer. Amongst the results, the lead compound can reduce the size of a tumor in an animal model by 90% within 25 days without apparent side effects.

Speaker
Biography:

Roberta Ettari in 2008 received her Ph.D. in Pharmaceutical Sciences at the University of Messina, she then worked as a postdoctoral researcher at the School of Chemistry (Galway, Ireland) and at Messina and Milan Universities. She spent also some research periods as guest scientist at Merck Research Laboratories (Pomezia), Instituto Grifols (Barcelona), Würzburg and Mainz Universities (Germany). In 2011, she received the “Farmindustria National Award for the Excellence in Medicinal Chemistry”. Since 2014, she is Assistant Professor of Medicinal Chemistry at the University of Messina working on the development of inhibitors of proteases involved in human and parasitic diseases. 

Abstract:

Neglected tropical diseases (NTDs) are a group of disabling infections particularly endemic in developing regions of Africa, Asia and the Americas. Over one billion people suffer from one or more NTDs, two of the most important are Human African Trypanosomiasis (HAT) and malaria. Although a number of antitrypanosomal and antimalarial agents are available, these suffer from problems like increasing drug resistance, toxicity and route of administration. Thus, there is an urgent need to identify new effective drugs, ideally directed against novel targets. The cathepsin L-like cysteine proteases rhodesain and falcipain-2 (FP-2), have been recognized as novel promising targets for the treatment of HAT and malaria respectively, because of their key roles for parasite survival.

The importance of rhodesain, a cysteine protease of T. brucei, is due to its several functions, such as its role in crossing the blood brain barrier, thus inducing the neurological stage of HAT; other functions include the turnover of variant surface glycoproteins that coat trypanosomes, degradation of host immunoglobulins to reduce the host immune response, and degradation of parasite and imported host proteins within lysosomes. On the other hand, FP-2, the main cysteine protease of P. falciparum, hydrolyzes hemoglobin to provide amino acids that are essential to the parasite for protein synthesis. FP-2 may also be responsible for the cleavage of the cytoskeletal proteins ankyrin and band-4.1 to facilitate rupture of the red-cell membrane. Thus, the development of novel rhodesain and FP-2 inhibitors is a promising challenge to obtain new effective agents for the treatment of HAT and malaria. 

Evgeny Pliss

P.G. Demidov Yaroslavl State University, Russian Federation

Title: Oxidative stress simulation by radical-chain oxidation of vinyl compounds
Speaker
Biography:

Evgeny Pliss has completed his Candidate of Science degree in 1978 and Doctor of Science in 1990. He has published more than 90 papers in reputed journals and is an author of several monographs. He is chair of General and Physical Chemistry at P.G. Demidov Yaroslavl State University.

Abstract:

A combination of microvolumetry, the rotating sector method, ESR, 1H-NMR, and IR allowed to establish a detailed mechanism of liquid-phase oxidation of vinyl compounds. A distinctive feature of the mechanism is the fact that the oxidation chain is carried out by a low-molecular hydroperoxide radical. Kinetic, correlation, and quantum-chemical analysis of these processes allows modeling the processes leading to oxidative stress in living organisms. The report analyses the routes of various chemical reactions that reduce the negative impact of oxidative stress. The study is proposes the use of a stable nitroxyl radicals of piperidine, pyrroline and imidazoline series as one of the effective components, leading to a positive effect.
The research is supported by RSF grant No. 14-23-00018.

Speaker
Biography:

Shouhong GAO has completed her Master degree of Pharmacy at the age of 27 year in Second Military Medical Univerisity. She has served as an associate Professor in Clinical Pharmacy for Drug Safety and Effectiveness since her graduation. For chemical drugs, she promotes better standardization of analytical practices in LC-MS based therapeutic drug monitoring analyses in clinical application. She has published more than 9 SCI papers as (co)first author, and was responsible for five funds as a project leader.

Abstract:

First-line anti-tuberculosis drugs are playing vital roles for curbing rapid spread of tuberculosis. mutidrug therapies are commonly applied in clinical to achieve better  treatment outcomes. However, drug resistance and adverse reactions came along with this therapies and therapeutic drug monitoring is a feasible way to precaution side effects. For this reasons, a simple and sensitive method based on LC-MS/MS and single protein precipitation was developed and validated for simultaneously quantifying of pyrazinamide, isoniazid, ethambutol, streptomycin and rifampicin in human plasma. Optimized chromatographic separation was achieved on a ZORBAX SB-C18 column with heptafluorobutyric acid, an ion-pair reagent, in the mobile phase at a flow rate of 0.3mL/min. The mass detection was achieved using electrospray ionization in the positive ion mode with a multiple reaction monitoring scan: m/z 124.1→79.1 for pyrazinamide, m/z 138.1→120.9 for isoniazid, m/z 205.3→116.2 for ethambutol, m/z 582.3→262.6 for streptomycin, m/z 823.4→791.2 for rifampicin and m/z 180.1→110.1 for phenacetin(Internal standard, IS). The LLOQ of pyrazinamide, isoniazid, ethambutol, streptomycin and rifampicin was 200, 80, 0.2, 2000, 200ng/mL, respectively. The Intra-day and inter-day accuracy and precision were within 15.0%. The method had been successfully applied to simultaneous determination of four first-line Anti-tuberculosis drugs in plasma from tuberculosis patients

Speaker
Biography:

Abstract:

The present work describes the preparation of protected octapeptide derivative (23-30) B-cain human insulin and coupling this peptide to B-chain desoctapeptide iodinated at tyrosine B16. B-chain will recombine with natural A-chain to give human insulin iodinated at tyrosine B16. Our approach of synthesis consisted of using stepwise coupling fragment condensation. All coupling was successfully with a high yield and easy to purify. For the side chain protection, we used (But) for OH-group of threonine and tyrosine, and (But) ester for C-terminal threonine. In most cases, Carbobenzoxy group was used for protection of N-terminal amino acids (Lys,Thr,Gly). Methylsulphonylethyloxycarbonyl (MSC) group was used for protection of NS-lysine.

Speaker
Biography:

Matthew D. Lloyd graduated with a DPhil from Oxford on clavulanic acid biosynthesis. Following post-doctoral research at Brown University, U.S.A. and Oxford, he took up a lectureship at the University of Bath in 2002. He is currently Senior Lecturer (Associate Professor) in Pharmacy & Pharmacology. Research interests include prostate cancer, chemical biology, lipid metabolism, enzymes and inhibitors as drugs. He has published >70 research papers and is an editorial board member of The Journal Of Enzyme Inhibition and Medicinal Chemistry and The World Journal of Biological Chemistry. He is also a 4th Black Belt (International Instructor) in the Ch’ang-Hon Taekwon-Do.

Abstract:

α-Methylacyl-CoA racemase (AMACR; P504S) catalyzes a key step in the degradation of branched-chain fatty acids and is important for the pharmacological activation of Ibuprofen and related drugs. Both the concentration and activity of AMACR are increased in prostate and other cancer cells, and the enzyme is a recognized drug target. However, all of the reported inhibitors are acyl-CoA esters (which do not comply with Lipinski guidelines) or non-specific protein modifying agents. Libraries of ~20,000 drug-like compounds were screened using a novel colorimetric assay; Incubation of R,S-2-3-(2,4-dinitrophenoxy)-2-methylpropanoyl-CoA with active AMACR resulted in the elimination of the strongly yellow 2,4-dinitrophenoxide and allows continuous measurement of activity in a microtitre plate format. Inhibitors were identified by a reduction in the rate of reaction in the presence of the library compound vs. the control. A number of novel reversible inhibitors were identified and their potency determined using dose-response curves. The results demonstrate the utility of the assay for the discovery and characterization of AMACR inhibitors as anti-cancer agents.

This work was funded by Prostate Cancer UK (PG14-009), a Biochemical Society Summer Vacation Studentship Award, The Nuffield Foundation and MRC technology.

Ivan Tikhonov

P.G. Demidov Yaroslavl State university, Yaroslavl, Russia

Title: Nitroxyl radicals as antioxidants against lipid peroxidation: an in vitro study
Speaker
Biography:

Ivan Tikhonov has completed his PhD at the age of 25 years from P.G. Demidov Yaroslavl State University. He is the senior lecturer in P.G. Demidov Yaroslavl State University. He has published more than 10 papers in reputed journals.          
 

Abstract:

Nitroxyl radicals (>NO·) exhibit a set of unique properties (ease of single-electron transfer, paramagnetic properties, cell permeability, antioxidant activity), which makes them attractive for use as drug components. It is known that >NO· catalytically dismute the superoxide anion, inhibit the oxidation of lipids, protect DNA from radicals. We investigated the mechanism of antioxidant action of nitroxyl radicals using a simplified model of lipid membrane (methyl linoleate (LH) in micelles). It has been established that >NO· effectively inhibit azo-initiated LH oxidation even at concentrations of ~10–6 M. Antioxidant activity of >NO· increases with increasing its lipophilicity. Each >NO· radical breaks 2-5 oxidation chains, i.e. the regeneration of antioxidant takes place. This effect is explained by the reaction >NO· + HO2· ® >NOH + O2, while HO2· radical is formed upon the LH oxidation in micelles. This conclusion is confirmed by the results of superoxide dismutase enzyme effect on the kinetics of the process: the antioxidant activity of >NO· decreases, and one >NO· radical terminates one oxidation chain, since the >NO· and HO2· interaction is eliminated. The piperidine-based radicals with a low reduction potential of the oxoammonium cation / nitroxyl radical pair, in particular 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), have the greatest antioxidant activity during the oxidation of LH in the presence of a source of O2·/HO2· radicals. This results can be useful for the selection of >NO· structures for testing as drug components to protect against the oxidative stress.
The research is supported by RSF grant No. 14-23-00018.

Margitta Dathe

Leibniz Forschungsinstitute of Molecular Pharmacology, Germany

Title: The secrets and potential of a novel cyclic antimicrobial and cell penetrating peptide
Speaker
Biography:

Margitta Dathe studied physics at the Humboldt University of  Berlin and completed her PhD in 1978 from the Academy of Sciences of the GDR. Since 1999 she has been working as head of the peptide-lipid interaction research group of the Leibniz Researchinstitute of Molecular Pharmacology. Her research interest is focused on targeting, cellular uptake promoting and antimicrobial peptides. She has published more than 100 papers in reputed journals.            
 

Abstract:

The development of antimicrobial peptides as antibiotic agents requires structural characterization and understanding of their diverse mechanisms of action. We investigated small cyclic anginine (R)- and tryptophan (W)-rich peptides characterised by variations in the amino acid position, exchange of  R and W by other charged or aromatic residues, introduction of D-amino acid residues and reduction and enlargement of the ring size. The cyclic hexapeptide cycloRRRWFW (cWFW) revealed high antimicrobial activity and proved to be not toxic against eukaryotic cells. Its amphipathic structure and arginine content provide the prerequisites for membrane permeabilisation and translocation as modes of action [1-3].Using a number of techniques to study peptide interaction with bacterial and eukaryotic cells and model membranes, we could show that the activity of cWFW is based on a novel antimicrobial mechanism. Strong interactions with the bacterial membrane lead to reduction in membrane fluidity and disturbance of the native lipid matrix. The formation of distinct lipid domains is related to a severe disturbance in the positioning of functional proteins [4]. Chemical modifications such as enhancement of the peptide hydrophobicity or enlargement of the cycle eliminated the bacterial selectivity and induced a membrane permeabilising mode of action. Although cWFW does not enter the cytoplasm of bacteria, it is rapidly internalized into human cells. The combination of cell penetrating properties with high antimicrobial activity and the novel mechanism of action render the cyclic hexapeptide an eligible compound with regard to the treatment of intracellular bacterial infections. 

Speaker
Biography:

Dr. Johann F. Osma has completed his PhD at the age of 28 years in Chemical Engineering from Rovira i Virgili University. He is an Associate Professor at Universidad de los Andes (Colombia) and head of the biomicrosystems research field from the microelectronics research center (CMUA) at the same university. He manages a clean-room specialized on biosensors and microfluidic systems dedicated to environmental monitoring, hazardous material detection, defense and aerospace. Also, he is the general secretary of the Colombian Nanoscience Network.

Abstract:

Point-of-care devices have emerged as a viable solution for the monitoring and diagnosis of different pathologies without medical intervention, and are meant to provide non-trained individuals with real-time diagnostic results. In general, point-of-care devices use a biosensor and an end-user device for the detection of a target analyte, e.g. proteins, cells, nucleic acids and metabolites, which can be related to a specific disease. Although there are many different techniques through which an analyte can be detected, immunoassays and electrochemical measurements have shown to be of special interest. In particular, electrochemical based point-of-care devices measure a change in the charge transport capacity between two electrodes via cyclic voltammetry, or a change of the electrical impedance via electrochemical impedance spectroscopy. Hereby, the design and fabrication of two different electro-immuno point-of-care devices for the detection of the human papilloma virus (HPV) and tuberculosis are presented. In both cases, a well array is placed on gold electrodes were specific antibodies are immobilized. Each well behaves as an individual biosensor through which electrochemical measurements are used to determine the presence of the target protein. The biosensors are integrated with an electronics reader that constitutes the end-user device, and are meant to be used by non-trained 

Speaker
Biography:

Roman Pliss has finished Yaroslavl State Technical University (Yaroslavl, Russia) in 1999. He has published more than 10 papers in reputed journals.

Abstract:

The role of the effect of nonspecific solvation in the addition of hydroperoxide radicals to π-bonds of trans-1,2-diphenylethylene and trans,trans-1,4-diphenylbutadiene-1,3 in the medium of different polarity solvents was investigated via a set of kinetic methods (microvolumetry, method of inhibitors, rotating-sector method). When the medium polarity is varied, the logarithm of the rate constant of this reaction in the Kirkwood-Onsager equation coordinates shows a linear dependence. Quantum-chemical analysis (NWChem, DFT B3LYP/6-311G**) allows us to conclude that the influence of the polarity of the medium for nonspecific solvation on the rate of the considered reaction will depend on how much the solvation energies of the transition complex and the initial reaction complex differ. If the solvation energy of the transition complex is higher than the solvation energy of the initial reaction complex, the reaction rate should increase with increasing solvent polarity, otherwise it should decrease.
The research is supported by RSF grant No. 14-23-00018.

Speaker
Biography:

Sandrine Ongeri has completed her PhD in 1999 from Université Paris Descartes (France) and postdoctoral studies from the University of Milano (Italy). During her PhD, she spent one year at Oxford University (UK). She is group currently leader at the University Paris Sud. Her group focuses on the design, the synthesis and biophysical evaluations of peptidomimetics as inhibitors of protein-protein interactions involving beta-sheet structures, in particular in amyloid proteins aggregation. Her group's research  is also expert in the synthesis of unantural fluorinated amino acids and in the use of fluorine as probe in peptide-protein interaction.

Abstract:

Amyloid fibrils are self-assembled insoluble aggregates that constitute the hallmark of more than 20 serious human amyloidosis diseases, such as Alzheimer’s disease (AD) and type II diabetes. Current drugs have failed to slow the progression of AD, which affects more than 35 million people worldwide. How drug candidates that reduce fibril formation act on the most neurotoxic oligomeric forms of amyloid peptide Aβ1-42 is far from being established. We report herein the capacity of two new classes of peptidomimetics to inhibit both Aβ1-42 early oligomerization and fibrillization: 1- sugar-based peptidomimetic analogs having physicochemical properties for drug-likeness[1]; 2- β-hairpin mimics[2]. A wide range of bio- and physico-chemical techniques, such as Thioflavin-T fluorescence spectroscopy, transmission electronic microscopy, a new developped capillary electrophoresis method[3], electrospray differential mobility analysis[4], nuclear magnetic resonance, and surface plasmon resonance, was used in order to identify the molecular mechanisms by which these new series of molecules can delay the aggregation of Aβ1-42. This is the first example of small molecules that preserves the non toxic monomeric species of Aβ1-42. Some compounds suppress totally the toxicity of Aβ1-42 towards SH-SY5Y human neuroblastoma cells, even at sub-stoichiometric concentrations. This protective effect is much more significant than that observed with molecules that have undergone clinical trials which reduce Aβ1-42 toxicity only at stoichiometric or higher concentrations. Preliminary results on the inhibition of IAPP aggregation involved in type II diabetes will be also presented.

Speaker
Biography:

Satoshi Mizuta received his Ph.D. at Nagoya Institute of Technology in 2008. He worked with Prof. Carlos. F. BarbasIII at The Scripps Research Institute. Then he went back to Japan to work at the Sagami Chemical Research Institute in 2010-2011. He joined the VG group as a Marie-Curie Fellow in September 2011 until May 2013, to work on the catalytic trifluoromethylation and the development of synthetic method for [18F]labelling. Satoshi is working at Nagasaki University, Japan. His current research interest is the drug design for antivirus. 

Abstract:

  Trifluoromethyl heterocycles have been an important motif of pharmaceutical drugs and agrochemicals because the presence of a CF3 group can cause the improved metabolic stability, lipophilicity and bioavailability. Nowadays, numerous CF3 substituted heterocycle-containing pharmaceuticals on the market can be witnessed, with examples such as trifluridine, efavirenz, celecoxib and mefloquin. Over the past decades, there has been an increasing interest in the development of method for the efficient synthesis of such fluorinated heterocyclic molecules as potential biological targets. Nevertheless, synthetic method accessing an array of CF3-containing heterocycles remains underdeveloped, in particular for nonaromatic heterocycles. Considering the difficulty of introducing CF3 moiety in nonaromatic ring systems, divergent synthesis using a simple and readily available CF3-containing precursor to convert into the diverse set of trifluoromethyl heterocyclic compounds may be one of the versatile and straightforward strategies for drug discovery. In this study, a series of α-trifluoromethyl α,β-unsaturated lactones and trifluoromethyl pyrazolinones were designed and synthesized. These two structural motifs of trifluoromethyl heterocycles were synthesized based on the synthetic pathway including a tandem stereoselective functionalization of the key precursor 3,3-dibromo-2-trifluoromethyl acrylic acid ethyl ester and intramolecular cyclization reaction. Further modification by Suzuki-Miyaura cross-coupling reaction provided a set of multi-functionalized α,β-unsaturated lactones and pyrazolinones. All synthesized compounds were bioassayed in vitro to determine their inhibitory activity against influenza A virus. We further modified a few potent hits in a viral inhibition assay and cunducted SAR studies on these scaffolds. The results showed that CF3-containing spirolactones possessed promising inhibitory activity being nearly active as oseltamivir.

Speaker
Biography:

Abstract:

Macrocyclic peptides now draw considerable attention as potential therapeutics due to their roles as mediators of key biological functions together with low toxicity and high specificity. Wellknown examples of cyclic peptide drugs include the natural antibiotic vancomycin, hormone oxytocine, neuropeptide vasopressin and antibiotics cyclosporine and tyrocidine A.1-3 A facile and economic strategy was developed to synthesize macrocyclic peptidomimetic
(compounds A and B) and naturally occurring Rolloamide A and B in a good yield. The substances showed strikingly high activity against Candida albicans and three Gramnegative bacterial strains. An excellent selectivity with respect to human cells was found, which implies low human toxicity.

 

Speaker
Biography:

Omer Abdalla Ahmed Hamdi  has completed his PhD from University Malaya, Malaysia. He is the director of Center of Natural Product Research and Drug Discovery,. He has published more than 12 papers in reputed journals and has been serving as supervisor for more than ten students for master and Ph.D program.        
 

Abstract:

 

Phytochemical investigation of C. zedoaria resulted in the isolation of 21 compounds. Isolated compounds includes eighteen sesquiterpenes and three labdane diterpenes. Various chromatographic techniques were used for the detection and isolation of the compounds. Extensive spectroscopic methods including NMR, IR, UV, GC-MS, LC-MS were used for the identification of the isolated compounds.  Isolated compounds were subjected to cytotoxicity, anti-oxidant and neuroprotective assays. Curcumenol and dehydrocurdione showed the highest protection (100%) against hydrogen peroxide induced oxidative stress in NG108-15 cells at the concentrations of 4 and 8 µM, respectively. In the oxygen radical antioxidant capacity assay, zerumbone epoxide showed the highest antioxidant activity with a Trolox equivalent (TE) of 35.41 µM per 100 µg of sample. In the MTT based cytotoxicity assay against four cancer cell lines (Ca 41 Ski, MCF-7, PC-3 and HT-29), curcumenone and curcumenol displayed strong antiproliferative activity (IC50 8.3 and 9.3µg/ml, respectively). A quantum chemical study was performed to investigate their relationship with cytotoxic activity and revealed that the dipole moment (µ), molecular volume (V), molecular area (A), polarizability (α) and hydrophobicity (log P) are the most important descriptors that influence the cytotoxic activity of the compounds under investigation. The two most active compounds; curcumenol and curcumenone were investigated for their binding to human serum albumin (HSA). The spectroflurometric analysis, in conjunction with molecular docking study suggested that both curcumenol and curcumenone could bind to binding sites I and II of HSA with intermediate affinity while site I was the preferred binding site for both molecules.

Speaker
Biography:

Tetsuo Narumi has completed his Ph.D at the age of 28 years from Kyoto University with Prof. Nobutaka Fujii. He spent a year in US as a JSPS postdoctoral fellow with Prof. Jeffrey W. Bode at the University of Pennsylvania. In 2009, he began his academic career in Japan, at Tokyo Medical and Dental University with Prof. Hirokazu Tamamura. In 2013, he began his independent career at Shizuoka University, in Japan, as an associate professor in the Bioorganic Chemistry. He has published more than 50 papers in reputed journals and serving as a leading researcher in the fields of peptidomimetic science.

Abstract:

Alkene-type dipeptide isosteres have emerged as ideal ground state mimetics of scissile peptide bonds. Although halo-substituted alkenes such as fluoroalkene and chloroalkene have been thought as one of the promising surrogates of peptide bonds, the lack of suitable synthetic methods toward those isosteres has hampered their application to pharmaceutical chemistry. To address this issue, we have identified a multi-gram preparative and diastereoselective synthetic approach toward (Z)-chloroalkene dipeptide isosteres [(Z)-CADIs]. A key to our approach is the use of 1,4-asymmetric induction strategy in the organocuprate-mediated allylic alkylation of allylic gem-dichlorides adjacent to the chiral center that is extremely useful for the diastereoselective synthesis of (Z)-CADIs in high yields with excellent (Z)-selectivity and diastereoselectivity (Z/E = >20:1, >20:1 dr) [Narumi, T. et al. Org. Lett., 2015, 17, 2302.]. In this presentation, we will demonstrate the preparation of several peptidomimetics containing (Z)-CADIs by utilizing our synthetic approach, and explore the potentials of (Z)-CADIs as amide bond isosteres including the H-bonding ability of the (Z)-chloroalkene moiety, the tolerance to Fmoc-solid phase peptide synthesis conditions, and application to the peptides for amyloid fibril formation.

Speaker
Biography:

Tove Tuntland holds a Pharmacy degree from the University in Oslo, Norway, and a Ph.D. in Pharmaceutics from the University of Washington, Seattle, USA. She has expertise in preclinical drug metabolism and pharmacokinetics (DMPK), pharmacology and PK/PD, and worked in discovery and development at Pfizer Global Research and Development (PGRD) in La Jolla, California (1996 to 2002). Thereafter until present time she has led a group at Genomics Institute of Novartis Research Foundation (GNF), supporting in vitro and in vivo preclinical DMPK and PK/PD studies in a variety of discovery and development programs in oncology, immunology, infectious and metabolic diseases. 

Abstract:

Successful drug discovery relies on selection of drug candidates with good in vitro ADME and in vivo pharmacokinetic properties as well as appropriate preclinical efficacy and safety profiles. However, in vivo animal pharmacokinetic studies are often conducted in a traditional low throughput manner, and therefore, are the bottlenecks of discovery projects in many pharmaceutical companies.

This presentation will focus on the tiered in vivo PK approaches, including snapshot PK, rapid PK and full PK study designs we have implemented to support our drug discovery efforts. In all 3 approaches, compound is dosed and analyzed discretely, thereby eliminating any drug-drug interaction concerns and analysis complications typically associated with cassette dosing or cassette analysis. The rapid PK approach uses several integrated and automated processes and sample pooling strategy to improve throughput, and has become our main stream in vivo PK approach in the lead optimization stage. These in vivo PK approaches differ in throughputs, capacities and the resources required, and are designed to address the varying needs of drug discovery projects at different stages of project progression. These approaches are well integrated within discovery research, allow tremendous flexibility and are highly efficient in supporting the diverse needs and increasing demand for in vivo profiling. Examples of each of the tiered in vivo PK studies will be illustrated.

Vasily Sen

P.G. Demidov Yaroslavl State University, Russian Federation

Title: Nitroxide-modified chitosans with enhanced antioxidant potential
Speaker
Biography:

Vasily D. Sen’ has completed his PhD at the age of 26 years from Institute of Organic Chemistry of Russian Academy of Sciences (RAS). Не is a head of Laboratory of stabile radicals in Institute of Problems of Chemical Physics of RAS. He has published more than 60 papers in reputed journals and is an author in several patents.

Abstract:

Chitosan is a biocompatible glucosamine polymer with properties suitable for a great variety of biomedical applications. Water-soluble at neutral pH chitosan-(poly)nitroxides (CPNs), differing in molecular weight of the saccharide backbone (Mw ~1 and ~10 kDa) and the nature of nitroxide radical (pyrroline and piperidine), were obtained and characterized. Fractions of modified glucosamines were in the range 0.15 – 0.28. The dependence of delay time of 2,2-azobis-2-methylpropanimidamide dihydrochloride (AAPH)-induced erythrocyte hemolysis on the concentration of CPNs and data of electron paramagnetic resonance (EPR) spectra indicate their binding to the cell membrane. Because of this binding, CPNs demonstrate identical delay times of hemolysis at concentrations ~100 times lower than structurally similar low molecular nitroxides. The proposed mechanism includes multiple breaking of oxidation chain through nitroxide oxidation to oxoammonium cations and reduction of the latter by common biological reductants. Due to easier oxidation of piperidine nitroxide by radicals RO2 to oxoammonium cations, CPNs with attached 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) more effectively inhibit hemolysis than their counterparts with 2,2,5,5-tetramethylpyrroline-1-oxyl. Work is in progress in designing of amphiphilic CPNs and CPNs with negatively charged groups (heparinomimetics), as well as nanostructures based on them. The effect of new materials on the viability of normal and tumor cells under oxidative stress will be investigated, as well as their use for drug delivery and cardiovascular applications.
The research is supported by RSF grant No. 14-23-00018.

Speaker
Biography:

Phil Page graduated from the Department of Chemistry, Imperial College London in 1975, and obtained his PhD from the same institution in 1978 under the supervision of Prof S V Ley. He spent two years working with Prof L A Paquette at Ohio State University as an SERC/NATO Research Fellow before moving to the University of Liverpool as a lecturer in 1983. He moved to the chair of organic chemistry at Loughborough University in 1996, and to the chair of organic chemistry at the University of East Anglia in 2007. He has published over 200 articles, and has won a Nuffield Foundation Science Research Fellowship, the Royal Society of Chemistry Hickinbottom Fellowship, the Royal Society of Chemistry Tilden Medal, the Glaxo-Wellcome Award for Innovative Chemistry, and a Royal Society Industry Fellowship. His research interests lie principally in asymmetric synthesis/catalysis, synthetic methodology and natural product synthesis. Prof Page, a Kentish Man, is married and lives with one wife and three cats. His hobbies include chemistry, reading, hi fi and music, not necessarily all at once, and food and drink. 

Abstract:

The development of methods for the introduction of asymmetry into organic molecules remains a topic of great importance. Catalytic systems are particularly desirable, and the combination of a catalytic asymmetric process with an environmentally friendly reaction system and an inexpensive oxidant offers an especially attractive goal. Non-racemic chiral epoxides are important intermediates for enantioselective carbon-carbon bond formation. We are developing organocatalytic systems in which asymmetric oxidants are formed by reaction of iminium salts with simple oxidants under mild conditions. We currently formulate the reactive intermediates as oxaziridinium ions, from which the iminium salt mediators are regenerated following oxygen transfer to alkene substrates. We can accomplish epoxidation of simple alkenes with up to ca 99% ee. Catalyst loading may be as low as 0.1 mol%. The epoxidation reactions may be carried out under aqueous or non-aqueous conditions. The iminium salt mediators can be easily prepared without chromatography in many cases, and the procedures used are simple to carry out, and require no preparation of unstable reagents. The lecture will discuss recent developments including new generations of catalyst, the first examples of kinetic resolution, the use of non-aqueous as well as the usual aqueous conditions, and alternative oxidants in place of Oxone, including hydrogen peroxide, bleach, and even electrochemical conditions by oxidant generation at boron-doped diamond electrodes. 

Speaker
Biography:

Dr. Piotr Przybylski, Chemistry Doctor's (Ph.D. - 2004) and Doctor Science (D. Sc.-2011) degrees at Adam Mickiewicz University in Poznan, now is an associate professor of organic chemistry, head of the research team at Faculty of Chemistry of Adam Mickiewicz University. He obtained „Maxima Cum Laude” award for best graduates of Faculty of Chemistry (2000) AMU Poznan, Stipend of President of Poznan city (2004), Award for Ph. D thesis of Prime Minister of Poland (2005), Award for Young Scientists (Warsaw 2005, 2006) and scholarship for research in West Pomeranian University of Technology of the Foundation for Polish Science (2007); postdoctoral researches in cooperation with Prof. F. Bartl from Charité – Universitätsmedizin, Institute Physik und Biophysik, Berlin and Humboldt Universität zu Berlin Lebenswissenschaftliche Fakultät Institut für Biologie, Berlin (2017, DAAD stipend), Germany. Currently Dr. Przybylski studies are focused on structure-activity relationships of natural products and their derivatives (macrolides, ionophore antibiotics and natural polyphenols) tautomerization, atropisomerization and proton transfer processes and the impact of these phenomenons on biological activity. Member of Ed. Board of Journal of Spectroscopy (since 2012) and Member of Committee of Chemical Sciences, Pol. Acad. Sci., Poznań Division (since 2011). He has published 106 papers in reputed journals.

Abstract:

Macrolide antibiotics are large group of natural products of attractive biological properties and produced by Streptomyces strains. Macrolides can be classified via inter-alia the type and the size of the macrolide ring1 as for e.g. lactone macrolides 14-membered erythromycins, 15-membered azithromycins, and 16-membered spiramycins and leucomycins, or lactam 26-membered rifamycins as e.g. rifampicine. Macrolide antibiotics, especially lactone ones, can be divided also by the type of saccharide moiety attached at the aglycone.2 Mechanism of action of macrolide lactone antibiotics’ is based on the inhibition of bacterial protein biosynthesis at different stages by reversible binding at bacterial 50S subunit of ribosomes3 whereas macrolide lactam antibiotics mechanism of action as rifamycins depends on inhibition of bacterial RNA polymerases4. Our modifications were performed using cascade and ‘click’ approaches in aim to construct novel semisynthetic antibiotics of well-balanced physico-chemical parameters (lipophilicity, water solubility) and of improved docking mode at the biological target. For example, modifications at aglycone ring via complete reconstruction of saccharides parts using regio- and diastereoselective cascade combination of  intramolecular esterifications, tandem E1cB eliminations and subsequent 1,2-addition to carbonyl followed by 1,6-conjugate addition at α,β,γ,δ – unsaturated aglycone yielded novel lactone macrolides of enhanced antibacterial and anticancer activities.5,6 We use also analogous combined cascade and ‘click’ approaches to modification of other group of natural macrolide antibiotics like lactone erythromycins to obtain alternatives to the currently used antibiotics in clinical therapy. The project is financially supported by Polish National Science Centre (NCN), decision number UMO-2015/19/B/ST5/00231.

Speaker
Biography:

Dr sundaram singh has completed her PhD at the age of 30 years from BHU, VARANASI . She is the Associate Professor of Chemistry Deptt, IIT(BHU),Varanasi. She has published more than 20 papers in reputed journals. Her research area is green synthesis, organic synthesis and evaluation of biological activity. 

Abstract:

An increase in regulatory limitations on the use, manufacture and disposal of perilous organic solvents has focused attention on the development of non-hazardous alternatives such as solvent-less synthesis, multicomponent reactions and reusable heterogeneous catalysts for the sustainable development of chemical enterprise. These organic reactions possess many advantages over traditional reactions in organic solvents. For example, solvent-less, multicomponent reactions with reusable heterogeneous catalysts reduce the consumption of environmentally hazardous solvents and minimize the formation of other waste. The reactions occur under mild conditions and usually require easier workup procedures and simpler equipment.

Nano zirconia (ZrO2) have been widely investigated in the past decades due to their multiple potential applications. The crystal phase of ZrO2 (monoclinic and tetragonal) strongly influences the catalyst activities and selectivities.

A highly efficient method for the synthesis of substituted imidazoles from a multicomponent reaction of isatin derivatives with ammonium acetate and aromatic aldehydes under solvent free conditions has been established. The reaction is supposed to proceed via nano ZrO2-catalyzed C=O bond activation followed by the formation of diamine intermediate and its condensation with ZrO2 activated isatin derivatives. Because of the simple and readily available starting materials, easy operation and high bioactivity of imidazoles, this strategy can be broadly applied to medical chemistry. The recyclability of the nano ZrO2 catalyst is another emphasis of proposed methodology.
Scheme 1: Synthesis of imidazole derivatives 4a-r via multicomponent reaction of isatin derivatives 1a-f with ammonium acetate 2 and substituted aromatic aldehydes 3a-f.

Speaker
Biography:

Yuegang Zuo is a Full Professor and Director of Graduate Programs at Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth. He received his B.S. degree in chemistry from Wuhan University in 1982, M.S. degree in environmental chemistry from the Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, in 1984, and PhD in environmental science from Swiss Federal Institute of Technology Zurich in 1992. Most of his recent research has focused on separation, identification and quantification of PPCPs and phenolic antioxidants in plants, pharmaceuticals, foods and the environment and examine their occurrence, sources, bioeffects and fate in the biochemsphere. 

Abstract:

Glimepiride is one of the most widely prescribed antidiabetic drugs and contains both hydrophobic and hydrophilic functional groups in its molecules, and thus could be analyzed by either reversed-phase high performance liquid chromatography (HPLC) or hydrophilic interaction liquid chromatography (HILIC) [Zuo Y (2014) (Eds.), High-Performance Liquid Chromatography (HPLC): Principles, Procedures and Practices. Nova Science Publishers, Inc., New York, USA; Zuo et al., Saudi Pharmaceutical J., 2017]. In the literature, however, only reversed-phase HPLC has been reported. In this study, a simple, rapid and accurate hydrophilic interaction liquid chromatographic method was developed for the determination of glimepiride in pharmaceutical formulations. The analytical method comprised a fast ultrasound-assisted extraction with acetonitrile as a solvent followed by HILIC separation and quantification. The effects of various HILIC parameters on the separation and determination will be discussed in details at the presentation. The developed method has been successfully applied to determine the glimepiride contents in pharmaceutical formulations and human fluids.

 

Speaker
Biography:

Jovana Bogojeski has completed her PhD diploma in 2012 under the supervision of Prof. Živadin D. Bugarčić at the Faculty of Science, University of Kragujevac and postdoctoral studies at the University of Braunschweig, Germany, in the group of Prof. Matthias Tamm. She is employed at Faculty of Science, University of Kragujevac as an assistant professor and her research activity is based on the study of kinetics and mechanism of chemical reactions of transition metal complexes with different biomolecules. She has published more than 20 papers in reputed journals.

 

Abstract:

A few novel rhodium(III) complex [RhIII(X)Cl3] (X = pyridin-bis(pirazole) ligands) were synthesized containing a pincer type, tridentate nitrogen−donor chelate system. All complexes were fully characterized, single crystal X-ray structure analysis has been done. The reactivity of the synthesized complex toward small biomolecules (L-methionine (L-Met), guanosine-5’-monophosphate (5’-GMP), L-histidine (L-His) and glutathione (GSH) and to a series of duplex DNAs and RNA was investigated. These measurements showed that the synthesized complex has a good affinity toward studied ligands and the obtained order of reactivity is: 5'-GMP > GSH >
L-Met > L-His. Duplex RNA reacts faster than duplex DNA, while shorter duplex DNA
(15mer GG) reacts faster compared with 22mer GG duplex DNA. In addition, a higher reactivity is achieved with a DNA duplex with centrally located GG-sequence than with 22GTG duplex, in which GG‑sequence is separated by a T base. Furthermore, the interaction of this metal complex to calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) was further examined by absorption (UV-Vis) and emission spectral studies (EthBr displacement studies). Overall, the studied complex exhibited good DNA and BSA interaction ability. All obtained results in this study indicate that the introduction of pincer-type spectator ligand can be used to improve the reactivity of rhodium(III) complexes. Together, these observations show the reactivity characteristics needed for a potential anti-tumor agent, with the ability to target both DNA and proteins. Every new contribution in this field highly is warranted due to the current lack of clinically used metallo-based alternatives to cisplatin. 

Victor Guallar

Barcelona Supercomputing Center, Spain

Title: PELE Studio: the next generation drug design software
Speaker
Biography:

Guallar completed his PhD in collaboration between UAB (Spain) and UCBerkeley (USA) and postdoctoral studies from Columbia University. After an assistant professor position at Washington University School of Medicine (USA), he was awarded an ICREA professor position at the Barcelona Supercomputing Center. He is also founder of Nostrum Biodiscovery. He has published more than 100 papers in reputed journals and has been the recipient of presitioug grants like an Advanced ERC from the European Union.

Abstract:

We are clearly assisting a rise of computational predictions in drug design; top pharmaceutical companies are signing large contracts with modeling software companies. This, has been made possible by the  improvement in the techniques (algorithms) but also by the rise in computational power, such as the use of graphic processing units (GPUs) in molecular dynamics of docking program.  Next generation drug design software, however, will embrace additional (current) technological developments. In this line we are combining PELE, our Monte Carlo sampling technique highlighted as an outstunding achievement in the latest CSAR blind test, with machine learning algorithms, high performance computing and improved 2D/3D visualization techniques.  Our aim is to provide a drug design software capable of: i) INTERACTIVE, instantaneous answers; ii) ACCURATE, quantitative answers; iii) SMART: self-learining capabilities; iv) CONNECTING: providing a virtual working space. Our efforts and initial results in this line will be provided in this talk.

Speaker
Biography:

Yahdiana harahap has completed her PhD from Department of Pharmacy, Institute Technology Bandung, Indonesia. Now she is the Head of Biavailability and Bioequivalence laboratory Faculty of Pharmacy, Universitas Indonesia. Prior to this position, she was the Dean of Faculty of Pharmacy, Universitas Indonesia. She has published more than 50 papers published in both International and National Journals. She has been invited to be the speakers in many international conference, especially in the field of BA/BE and Bioanalysis technique. She currently serves as an expert at Indonesia National Agency of Drug and Food Control, spesifically in BA/BE evaluation.

Abstract:

Lercanidipine is an antihypertensive of calcium channel blocker that is effective in treatment of patients with mild to moderate hypertension without affecting heart rate. The aim of this study was to obtain the optimum method and validate lercanidipine analysis in plasma using LC-MS/MS. Chromatographic separation was performed using Waters AcquityTM UPLC C18 1.7 µm (2.1 x 100 mm) column with mobile phase a mixture of 0.1% formic acid - methanol (20:80 v/v) with isocratic elution, the column temperature was 30°C with 0.2 mL/min flow rate and amlodipine as internal standard. Mass detection was performed on Waters Xevo TQD equipped with an electrospray ionization source in the MRM mode. Lercanidipine was detected at m/z 612.11 > 280.27 and amlodipine was detected at m/z 409.1 > 238.15. The optimum sample preparation was carried out by liquid-liquid extraction method using 5 mL mixture of n-hexane-ethyl acetate (50:50 v/v), vortexed for 3 mins, centrifuged at 4000 rpm for 20 mins, evaporated at 50°C for 30 mins, and reconstituted with 100 µL of mobile phase. This method was linear at concentration range of 0.025 to 10 ng/mL with r ≥ 0.9986, and fulfills the acceptance of accuracy and precision within and between run in three days. In addition, this method fulfills the acceptance criteria for selectivity, carry over, stability, dilution integrity and matrix effects based on Guideline on Bioanalytical Method Validation by the EMA in 2011.

Speaker
Biography:

Dr. Bhattacharjee currently an Adjunct Faculty Professor has over 25 years of research experience in quantum chemistry, pharmacophore modeling, and virtual screening of compound databases. His experiences cover drug discovery programs for antimalarials, antileishmanials, insect repellents and counter agents against OP poisoning. Current interests are in the discovery of antivirals targeting dengue, West Nile and Zika viruses. He has authored and coauthored over 120 publications, three book chapters and 5 patents. Prior to joining the Georgetown University, he served in the Walter Reed Army Institute of Research, Silver Spring, Maryland (U.S.A.) as the Chief Molecular Modeler for drug discovery programs.

Abstract:

Organophosphorus (OP) compounds such as tabun, soman, DFP, sarin, cyclosarin and some pesticides are highly toxic group of compounds. Of the OP-agents, tabun (GA) is the most toxic and developing antidotes for it is a challenging problem. However, tabun being a G –simulator, less toxic DFP is frequently used in experiments for discovery of new reactivators. Using in silico strategy from our previously reported pharmacophore model containing a hydrogen bond acceptor, a hydrogen bond donor, and an aromatic ring (Chem Res & Toxicol, 2010, 23, 26-36), we discovered 17 non-oxime reactivators for DFP-inhibited AChE from a virtual screening of in-house database and two commercial databases, Maybridge and ChemNavigator. All these non-oximes contained a nucleophile group in lieu of the oxime moiety and none was reported before to have potent reactivation efficacy. Efficacy (kr) of all the 17 non-oximes were found to be within 10-fold of 2-PAM in an eel DFP-inhibited AChE in vitro assay. One the non-oximes showed in vivo efficacy comparable to 2-PAM against brain symptoms for DFP-induced neuropathology in guinea pigs. Moreover, two of them showed promising results with no major differences in brain restoration of AChE activity compared to 2-PAM after DFP exposure. Since a serious loss of cholinergic function in the central nervous system contributes significantly to the cognitive symptoms associated with AD and other advanced age related brain diseases, these results on competitive OP-inhibited AChE reactivation and inhibition behavior of non-oximes may be useful for further neurological therapeutics studies.

Speaker
Biography:

Daisuke Yamamoto has completed his PhD in 2006 at Kitasato University (Prof. Toshiaki Sunazuka). Subsequently, he became a researcher at the Kitasato Institute (Prof. Satoshi Ōmura) and joined the group of Prof. Barry M. Trost at Stanford University, as a postdoctoral fellow. In 2008, he started his academic career as an Assistant Professor at Kitasato University. His research focuses on the development of redox reactions with attendant applications in biologically active molecules.

Abstract:

Developing a new methodology for transition metal-catalysed oxidation reactions has been extensively studied in the recent decade, and molecular oxygen is essentially recognised as an ideal oxidant. Despite developing several elegant oxidation processes involving molecular oxygen as a sole oxidant, methodologies for directly incorporating molecular oxygen into organic substrates remains a major challenge in synthetic chemistry. In continuation of our studies on manganese-catalysed oxidative reactions, we have found that manganese(III) acetylacetonate is a highly efficient catalyst for hydroperoxidation of carbon-carbon double bonds of enynes as well as styrene derivatices using N-hydroxyphthalimide, N-hydroxybenzotriazole or N-hydroxysuccinimide under mild reaction conditions. This reaction proceeded at room temperature through the direct incorporation of molecular oxygen present in air. The required catalytic loading of manganese(III) acetylacetonate is extremely low (generally 0.02–0.5 mol%, and a minimum of 0.001 mol%). On the basis of this knowledge, we recently reported a manganese-promoted oxidative cyclisation of unsaturated oximes to provide 4,5-dihydroisoxazoline alcohols. In addition, we applied our method to the synthesis of hydroxamic acid, which is a promising antitrypanosomal agent for the management of Chagas disease. In the presentation, we will also discuss the further studies.

Speaker
Biography:

Shaaban K. Mohamed has completed his PhD at the age of 32 years from Minia University and postdoctoral studies from Didsburg University School of Chemistry, Germany and Manchester Metropolitan University, UK.. He is member of RSC and received  the Knowlege Exchange award 2013, MMU, UK .  He has published more than 260 papers in reputed journals and has been serving as an editorial board member of repute  journals such as International Journal of Chemistry and Pharmaceutical Research, Greener Journal of Pharmacy and Pharmacology, and Journal of Pharmaceutical and Applied Chemistry.
 

Abstract:

The emergence of multidrug resistant (MDR) bacteria has necessitated the development of novel groups of antibiotics that effectively block or subvert bacterial growth [1,2]. It has been reported that different efforts and diverse investments have been made to develop novel strategies for improving the concept of antibiotic delivery that could enhance the limited activity of those vital antibiotics against such types of bacteria [3,4]. In the present study, amoxicillin trihydrate and Neomycin sulphate were used for the first time as both reducing and capping agents in synthesis of silver nanoparticles (AgNPs). The synthesized AgNPs were evaluated for their antibacterial and synergistic activity with antibiotics against selected human pathogenic bacteria.

 

Speaker
Biography:

Mariola Napiórkowska is  Ph.D on the Chair and Department of Biochemistry of Medical University of Warsaw. She has working at the Warsaw Medical University for 18 years.  For many years she has engaged on the synthesis of compounds with biological activity. She is co-author of 23 publications and two patent applications. 

Abstract:

The growth rate of the number of cancer cases is enormous and requires intensive research and introduction of new anticancer drugs. Ideally, these new drugs should possess improved pharmacokinetic parameters and high selectivity towards cancer cells providing less negative side effects. The present work describes the synthesis and cytotoxic activity of a large group of new derivatives of dicarboximides. In our previously studies with this group of compounds we have identified several derivatives that presented highest cytotoxicity to leukemia cells, lines K562, HL-60, respectively (IC50* in the range of 1-10µM). On the contrary, these compounds were non-toxic to non-tumor endothelial cells (HUVEC) and tumor adherent cells (HeLa). Taking into account the high activity of evaluated compounds, we decided to continue our work on the field of these derivatives. The main stage of synthetic works was the modification of the structure of dicarboximides in order to obtain  products with improved solubility and bioavailability, while retaining their biological activity. In order to improve the solubility of the compounds hydrophilic groups such as -OH, -NH2, -NH-R were introduced to their structure. Thus we have synthesized 33 new derivatives.  The structures of all new compounds were established by  1HNMR, 13CNMR and HR MS spectra. The obtained compounds were tested for their cytotoxic properties in cervix carcinoma (HeLa), chronic myelogenous leukemia (K562), acute lymphoblastic leukemia (MOLT-4)  and normal endothelial (HUVEC) cells using MTT assay. In these screening studies we have identified 28 compounds that showed toxicity toward both HeLa, K562 and MOLT-4 cell lines. 

Speaker
Biography:

Prof. Sartaj Tabassum is working as Professor in the Department of Chemistry, Aligarh Muslim University, Aligarh and  Presently in King Saud University ,Riyadh Saudi Arabia He has published 105 papers in the journals of international repute. He is a life member of ICC, CRSI, ISCB, DNA Society of India and American Nano Society. He has successfully guided 16 Ph.D. He has successfully completed many research schemes granted by TWAS, Italy, CSIR, New Delhi, DBT, Govt. of India. As a distinguished Scientist, Prof. Tabassum was awarded Overseas Associateship award in 2005 by DBT, Govt of India. He has signed several MoU and joint research collaboration with University of Camerino UNICAM, Italy, USM Malaysia and USTC Hefei, China. He has visited many countries for academic pursuit particularly, China, USA, Italy,Saudi Arabia  as fellow, visiting Professor and for the international conferences. 

Abstract:

Medicinal inorganic pharmaceutical chemistry is an interdisciplinary thrust area of chemical biology research; is currently much more known for its many applications in enzyme mimic catalysis and also has enormous potential to act as therapeutic and diagnostic agents Development of new drug design and therapeutic strategies that could target cancer cells leaving normal cells unaffected still continues to be a challenge. Series of New pharmacophore of metallic compounds were designed, synthesized and characterized by various spectroscopic methods (IR, ESI–MS, 1H, 13C and Sn119 NMR) and further confirmed by X–ray crystallography. In vitro DNA binding studies of the compounds investigated by absorption and emission titration methods which revealed that 1 recognizes the minor groove of DNA in accordance with molecular docking studies with the DNA duplex. Gel electrophoretic assay demonstrates the ability of 1 to cleave pBR322 DNA through hydrolytic/oxidative process which were further validated by T4 religation assay. To understand the drug–protein interaction of which ultimate molecular target was DNA, the affinity of compounds towards HSA was also investigated by the spectroscopic and molecular modeling techniques which showed hydrophobic interaction in the subdomain IIA of HSA. The SOD-like activity of the compounds was  evaluated using a xanthine/xanthine oxidase assay, which showed SOD activity in the micro molar range for both the heterobimetallic complexes viz., (IC50) 0.082 μM. Furthermore, complexes showed high inhibitory activity against Topo-Iα at a concentration of 20 μM as IC50, suggesting that complex  is an efficient DNA cleaving agent. In vitro studies on the anticancer activity against the HepG2 hepatocellular carcinoma cell line revealed that complexes have the capability to kill the chosen cancer cell, but the efficiency of  few complexes  are higher than the reported earlier . The mode of cell death induced by complex  is primarily apoptosis as revealed by AO/EB staining, Hoechst 33258 staining, and assessment of the mitochondrial trans-membrane potentia

Speaker
Biography:

Dr. Jim-Min Fang received his PhD degree in 1980 from Yale University. After finishing his postdoctoral research, he joined the Department of Chemistry, National Taiwan University (NTU), as Associated Professor in 1982. He is now an NTU Distinguished Professor and TBF Chair in Biotechnology. He also holds a joint appointment in the Genomics Research Center, Academia Sinica. His research interests are organic synthesis and chemical biology. He has published more than 250 papers. 

Abstract:

Vaccination and drugs are effective for prevention and treatment of seasonal flu. However, drugs are especially needed in pandemic influenza before new vaccines can be produced. Influenza A is the most infectious type of influenza viruses. There are 18 subtypes of hemagglutinin (HA) and 11 subtypes of neuraminidase (NA). Avian influenza viral HA recognizes the 2,3-linked sialic acid receptor on the host cell surface, whereas human influenza viral HA recognizes the 2,6-linked sialo-glycoprotein receptors. NA is reponsible for breaking the connection between viral HA and the host cell, so that the progeny virus particle can be released to infect the surrounding cells. Pandemic influenza infection may occur due to the genetic reassortment of HA and NA. Inhibition of NA is thus a useful strategy in development of anti-influenza drugs. Zanamivir (RelenzaTM), oseltamivir (TamifluTM) and peramivir (RepiactaTM) are the NA inhibitors used for treatment of influenza. However, the on-market anti-influenza drugs still have shortcomings, such as the emergence of oseltamivir-resistance viruses, and non-oral availability of zanamivir and peramivir. In this presentation, we shall show the use of phosphonic acid as a bioisostere of carboxylic acid for developing more effective anti-influenza agents. 

Speaker
Biography:

Nadezhda Shchepina has completed her PhD at the age of 28 years from Leningrad (St. Petersburg) State University, Department of Radiochemistry. From 1972 year she works at the Laboratory of Radiochemistry of Perm State University (Scientist 1972-1980, Senior Scientist 1980-2002, Head of the Laboratory of Radiochemistry 2002-current). She was Visiting Associative Professor of Chemistry at Creighton University, Omaha, NE, USA (1978-1979). She defended the Doctoral Dissertation (Radiochemistry & Organic Chemistry) at Moscow M.V. Lomonosov State University in 2013 year. She is Full Professor at the Department of Organic Chemistry of Perm State University (2014-current). Nadezhda Shchepina has published more than 180 publications (24 patents of the USSR and 8 patents of Russin Federation, 85 articles in Russian and foreign reputed scientific journals).

Abstract:

A simple glance at databases of approved pharmaceuticals reveals the structural significance of nitrogen-based heterocycles in the drug design and engineering of pharmaceuticals, with nearly 60% of unique small-molecule drugs containing a nitrogen heterocycle. The pyridine ring can be considered one of the most simple, but at the same time one of the most important heteroaromatic structure. Many biological processes in the organism involve participation of compounds containing a pyridine structure, such as nucleic bases, ferments and enzymes. Moreover, conducted biological studies showed that the most promising and, in some cases, unique, are quaternary pyridinium derivatives. A major synthetic obstacle to accessing variously substituted pyridines is the fact that in the classical organic chemistry reaction of direct phenylation of the heterocyclic nitrogen atom is unknown and the quaternary aryl derivatives may be prepared only through a cyclization reaction. New features offers elaborated by us nuclear chemical method, namely, the use of the revealed reaction of direct heterocyclic nitrogen atom phenylation by nucleogenic (generated via tritium beta decay processes in tritiated benzene) free substituted and unsubstituted phenyl cations in order to obtain both inaccessible and unknown in the classical organic chemistry phenyl substituted six membered heterocyclic structures with quaternized nitrogen atom; one-step production of tritiumlabeled biomarkers with fixed tritium label in N-phenyl ring; and the study of pharmacological action of promising compounds with quaternary nitrogen scaffold by tritium label.

 

Speaker
Biography:

After completing a PhD at the University of Alcalá, Madrid (Spain) in 2013, Marco Marazzi was a Humboldt Fellow at the Karlsruhe Institute of Technology (Germany). Starting from 2015, he is a researcher at the French National Center for Scientific Research (CNRS) and at the University of Lorraine in Nancy (France). Always interested in photoinduced processes of biologically relevant systems, he studied especially organic molecular switches applied to peptide conformational changes, channelrhodopsin as an optogenetic tool, and DNA photosensitization via Type I and II processes. His expertise covers a broad range of modeling techniques. 

Abstract:

Although diverse DNA photostability mechanisms exist, organic dyes in the vicinity of DNA can induce damages through indirect light absorption. Hence, understanding the underlying mechanisms involved in photosensitized DNA damage is crucial to describe and possibly anticipate photobiological risks, as well as to design anticancer phototherapies. Here, we present the results concerning our latest studies on different reactivities induced by common organic dyes, through multiscale molecular modeling techniques coupled to spectroscopy experiments. Especially, the photochemistry of benzophenone – a paradigmatic DNA photosensitizer – and its implications in the competitive processes of hydrogen abstraction and energy transfer to DNA will be described. Electron transfer is also considered by the interaction of DNA with two fluorescent dyes widely used in cellular biology: nile blue and nile red. Finally, the potentialities of a very recently sinthesized novel carbazole in photosensitizing DNA through two-photon absorption will be reported. Especially, it will be shown how it can induce DNA strand break upon photoionization with the production of a solvated electron. The main advantage is the low-energy (infra-red) irradiation required also in the absence of molecuar oxygen,  i.e. a  prodrug of great interest for the potential treatment of solid tumors.          

Gabriela Pricope

Centre of Advanced Research in Bionanoconjugates and Biopolymers, Romania

Title: Supramolecular G-quartet architectured hydrogels as drug delivery systems
Speaker
Biography:

Supramolecular hydrogels have been extensively studied for their biomedical and pharmaceutical applications. Proprieties such as high water content and the soft consistency, similar to the consistency of natural tissue, contributes to their biocompatibility. Furthermore, the ability of different sized molecules to diffuse into (drug loading) and out of hydrogels (drug release) make these materials perfect candidates for drug delivery systems. In this report, hydrogels based on the formation of G-quartet were proposed and studied for the incorporating and releasing of the active compounds. An in situ method for drug loading was selected, thus the hydrogel network formulation and the drug encapsulation were accomplished simultaneously. The release of the encapsulated compounds was determined by diffusion in buffer solutions at physiological and acidic pH values. Drug-release measurements were performed using UV-Vis spectroscopy, fluorometry and circular dichroism spectroscopy. Presented work also shows the influence of structural components upon drug loading/release properties of the newly prepared hydrogels.

Abstract:

Gabriela Pricope is a biology graduate, with a master’s degree in microbial and cellular biotechnologies, currently PhD student in chemistry at ‘‘Petru Poni’’ Institute of Macromolecular Chemistry.

Alexander V. Sirotkin

Constantine the Philosopher University and Research Institute of Animal Production, Slovakia

Title: Plant molecules affecting female reproductive functions
Speaker
Biography:

Prof. A.V. Sirotkin, PhD, DrSc is working as Professor at the Constantine the Philosopher University, as a Research Scientist at Research Institute of Animal Production in Nitra and as a Visiting Professor at the King Saud University in Ryiadh. He has about 600 publications including 120 full papers in the international journals. He is a member of editorial boards of 4 international journals and a recipient of more than 10 national and international awards.

Abstract:

The aim of our in vitro and in-vivo studies was to examine the potential influence of some medical and food plants and their constituents on ovarian functions and their potential usefulness as pharmacological stimulators of fecundity and protectors against the influence of environmental contaminants.  For this purpose, we have study the influence of green tea, rooibos, ginkgo, flaxseed, yukka extracts, as well as of plant molecules resveratrol, curcumin, quercetin, daidzein, diosgenin on proliferation, apoptosis, release of hormones and response to gonadotropins of murine, porcine and rabbit ovarian cells as well as on rabbit fecundity.  It was observed, that green tea, rooibos, ginkgo, flaxseed, extracts, as well as of resveratrol, curcumin, quercetin, daidzein, diosgeninare able to suppress proliferation, promote apoptosis, to alter the release of steroid hormones and to inhibit the response of cultured ovarian cells to hormonal stimulators FSH and IGF-I. On the other hand, some of these plants were able to prevent the action of environmental contaminants benzene, xylene and toluene on ovarian cells.  Yucca extract expressed an opposite effect. Furthermore, feeding of rabbits with yucca and curcumin increased their fecundity. These observations suggest potential direct inhibitory influence of food and medical plants green tea, rooibos, ginkgo, flaxseed on ovarian functions. The similarity in plant and plant constituents effects suggest that the observed plant effects can be due to presence of curcumin, quercetin, daidzein and diosgenin. The potential anti-reproductive effect of these plants should be taken into account by their consummation. On the other hand, some plants or plant molecules could be used as stimulators of reproduction and fecundity and protectors against the influence of environmental contaminants.

Speaker
Biography:

Prof. Danagulyan has completed his PhD at the age of 27 from M. Lomonosov Moscow State University, in 2000 defended  ScD thesis in Yerevan. Elected Corresponding Member of the National Academy of Sciences of Armenia (2010). Research areas: Chemistry of nitrogen-containing heterocycles and of biologically active substances. He has published more than 200 papers in reputed journals and is a member of editorial boards of a number of journals.

Abstract:

Compounds containing condensed pyrimidine systems and a bridged nitrogen atom are known to present interest as potential analgetics, antitumor drugs, bronchial spasmolytics and breathing stimulants. They form the composition of some drugs. We studied the reaction of 2-(ethoxycarbonyl)methyl-1,4,6-trimethylpyrimidinium iodide with hydrazides of C-pyridyl-,  C-pyrimidinyl-, N-azolyl- and C-pyrazolyl-substituted carboxylic acids. This reaction was shown to result in recyclization and formation of ethyl 2-(pyrimidinylalkyl)- and 2-(azolylalkyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylates. It is a new rearrangement of 1,2-dialkylpyrimidinium salts proceeding through the pyrimidine ring recyclization with inclusion of the nucleophilic reagent fragment into the transformation product.  Heterocyclic acids hydrazides, in which a hydrazide fragment is immediately connected with a heterocyclic ring, also undergo a similar reaction. By the reactions of salt 1 with isonicotinic acid hydrazide (isoniazid) and pyrazol-3-carboxylic acid hydrazide we managed to obtain pyrazolo[1,5-a]pyrimidine derivatives that contained in position 2 pyridine and pyrazole rings. Besides pyrazolopyrimidines, the separation of reaction mixture provided in some cases also another recyclization product, 2-hydroxy-5,7-dimethylpyrazolo[1,5-a]pyrimidine.

Speaker
Biography:

Dr. Adriano Mollica is currently Associate Professor of Medicinal Chemistry at the Univ. “G. d’ Annunzio” of Chieti-Pescara, Italy and PhD in “Pharmaceutical Sciences. His research interests are focused on opioid peptides, neurodegeneration, treatment of chronic and neuropathic pain, multi-target compounds and nutraceuticals developments. He is co-author of 90 papers, one European Patent, two books and several oral communications. He is currently Editor in Chief of Current Bioactive Compounds and EBM for Mini Rev. in Med. Chem., Frontiers in chemistry (Medicinal and Pharmaceutical Chemistry), Prot. & Pept. Lett. and LDDD.

Abstract:

Novel cyclic analogues of enkephalin containing xylene bridge regioisomers  (7a-c) have been synthesized and fully characterized as mixed m,d opioid receptors agonists.a,b The in vitro activity has been investigated showing a good affinity of 7a-c for both of them. In vivo biological assays revealed that 7b is the most potent cyclic analogue with the ability to maintain high level of analgesia after 60 and 90 minutes following i.c.v. and i.t. administrations respectively in Tail Flick test and long lasting analgesia after subcutaneous administration.

Speaker
Biography:

Christian Cavé has completed his PharmD at the age of 22 years from University of Paris Sud and this PhD at the age of 29 years from University of Paris Sud (France).  In 1997 he was full professor  of Organic chemistry at the University of Burgandy then since 2002 he is full professor at the Faculty of Pharmacy, Uniserty of Paris Sud. He was director of a research team focusing on the asymmetric synthesis and Medicinal Chemistry and currently he works in the team "Chimiotherapie Antiparasitaire" UMR CNRS BioCIS.

Abstract:

 Leishmaniasis is a neglected tropical disease who occurs in 88 countries and infects 12 million people worldwide that causes hundreds of thousands of deaths per year. Only few treatments are currently available (i.e. antimonials, miltefosine and AmBisome®) while more and more cases of drug resistance appear all around the world. To overcome the limitations of these treatments, we have started to develop a new series of inhibitors of an original target that are essential for parasite survival or virulence : the GDP-Mannose Pyrophosphorylase(GDP-MP), an enzyme involved in glycosylation and essential for amastigote survival. The goal of this project is to develop inhibitors that are specifically active on the GDP-MP of Leishmania infantum and do not have side effects on the human homologous enzyme. Currently we are working on click chemistry in order to synthesize stable analogs of GDP-MP in Medicinal Chemistry,

Speaker
Biography:

Carlos Tomich has completed his PhD at the age of 31 years from University of São Paulo and postdoctoral studies from University of São Paulo and PRBB, at Barcelona-Spain. He is the Associate Professor of Pharmaceutical Chemistry at University of São Paulo, with a drug design research position. He has published more than 120 papers in reputed journals and has been serving as an editorial board member of repute. 

Abstract:

Aryl hydrocarbon receptor (AhR) is a transcription factor activated by ligand. However, AhR also modulates many physiological and pathological processes that affect inflammatory and immunological responses. There is a growing interest in discovery of selective competitive antagonists for AhR, where the most potent ones exhibit acceptable antagonist properties but they also show partial agonist activity or exhibit agonist activity on estrogen receptors (ER). Also, limited availability of selective and pure competitive AhR antagonists and scarce structural information regarding AhR binding domain (located in the PAS-B domain) are reported. In this work, a preliminary search in the Protein Data Bank (PDB) for AhR structures revealed only one – a PAS-A domain, but not PAS-B. A homology model of the PAS-B domain of the AhR receptor was then carried out, using PAS-B structures of ARNT as templates. A flexible docking approach was then used with the most potent AhR antagonists reported, allowing us to derive (and to validate) a pharmacophoric pattern common to the compounds thus aligned. Two subsequent virtual screening experiments were then performed in databases of commercially available compounds, using: (1) the pharmacophore model; (2) the shape and electrostatic potential of the most potent AhR antagonist reported. In sequence, 29 compounds were filtered regarding to both atoxicity and good pharmacotherapeutic profile, thus predicted in silico. Finally, at least 5 novel atoxic AhR antagonists have been discovered, which experimentally showed atheroprotective efficacy correlated to the AhR antagonism, since they inhibited, almost completely, AhR-mediated oxLDL uptake by murine macrophages, induced by TCDD.

Speaker
Biography:

Abstract:

BIIB042, a g-secretase modulator, was pursued for its potential in the treatment of Alzheimer’s Disease.  Med. Chem. synthesis consisted of four chemical reactions.  A mixture of four diastereomers were made in the first step and carried through to the end of the synthesis.  BIIB042 was obtained in ~4% overall yield via chiral HPLC separation.  A seven-step process was developed for delivery of kilograms of BIIB042.  A racemic mixture made in the first step was separated using SMB chromatography.  Second chiral center was introduced in the last step by stereoselective hydrogenation reaction to afford BIIB042 in 95-96% ee. This route afforded the API in ~9% overall yield. Further improved synthesis included synthesis of by Petasis reaction of enantioenriched aldehyde 1 followed by its conversion into BIIB042 in two steps (Scheme 1).  Development of a mild and efficient Petasis reaction condition made synthesis of in high yield without loss of ee possible.  This new Petasis reaction condition was applicable to a variety of substrates (Shi, X, et al. J. Org. Chem. 2012, 77, 1154).  

Speaker
Biography:

Ph.D. from University of Tokyo (in Pharmaceutical Sciences) in 1972. Research Associate at NIH (1973-80), Group leader at Max-Planck-Institute for Biochemie (1980-1984). Senior Scientist at Yale University and UCSD (1985-88). Laboratory Head at Ludwig Institute for Cancer Research (Melbourne Branch) (1988-2006). Visiting Professor at Hamburg University Hospital (2006-2007). Manager at PAK Research Center in Melbourne (2007-present). 

Abstract:

PAK1 (RAC/CDC42-activated kinase 1)  is the major oncogenic/ageing kinase that is responsible for a wide variety of  diseases/disorders such as cancers, neurofibromatosis (NF), Alzheimer’s disease (AD), diabetes (type 2), hypertension, a variety of infectious and  inflammatory diseases, epilepsy, schizophrenia, depression, autism, and obesity. In addition, PAK1 shortens the healthy lifespan (1), and is essential for PDGF-dependent melanogenesis as well (2), suggesting that PAK1-blockers could be elixirs and skin-whitening cosmetics. It should be worth noting that all herbal AMPK activators are PAK1-blockers as well as HSP (heat shock protein)-inducers, as the anti-oncogenic kinase LKB1 activates AMPK as well as inactivates PAK1, and activates HSP genes through the transcription factor FOXO that is activated by AMPK and inactivated by PAK1 (1).   Thus, the potential market value of natural or synthetic PAK1-blockers/AMPK activators/ HSP-inducers would be huge, and pharmaceutical giants such as Pfizer, Roche, Novartis and Astrazeneca recently started developing potent PAK1-blockers. However, major problem of these synthetic PAK1-blockers for clinical application is their poor water-solubility and cell-permeability. Here we present a new trick for robustly boosting the anti-cancer activity and cell-permeability of several COOH-bearing PAK1-blockers without any loss of their water-solubility. According to Barry Sharpless (2001 Nobel-laureate), any COOH-bearing compounds could be esterized with water-soluble 1,2,3-Triazolyl alcohol through copper-catalyzed  “Click Chemistry” (CC) in a high yield. Thus, in 2015, we have successfully synthesized 1,2,3-Triazolyl esters of  two herbal PAK1-blcokers (artepillin C, ARC, and caffeic acid, CA) from propolis, and an old pain-killing PAK1-blocker (ketorolac) sold by Roche. The resultant esters (15A, 15C and 15K) are highly cell-permeable and  their anti-cancer activity is 100 times of ARC, over 400 times of CA, and over 500 times of Ketorolac, respectively (3). Among these esters, 15K is the most potent anti-cancer/PAK1-blocker with IC50 =24 nM (against A549 lung cancer) and IC50=6 nM (against B16F10 melanoma) cells (3). Furthermore, 15K inhibits angiogenesis in ovo (fertilized eggs) with IC50 = 1 n mole/egg (Ahn, MK et al, unpublished observation). Currently we are testing if 15K extends the healthy lifespan of C. elegans, as does Okinawa propolis (OP) (4). Regarding OP and edible sea cucumber (SC), the major anti-cancer ingredients of OP and SC are geranylated flavonoids (Nymphaeols A-C), and a sulfated saponin called Frondoside A (FRA), respectively.  We recently found that both Nymphaeols and FRA directly inhibit PAK1 in vitro with IC50 10 mM and 1 mM, respectively, in a selective manner (Nguyen, BC et al, unpublished observation). 

Speaker
Biography:

Abstract:

In this work we derive the generalized Hamilton–Jacobi equations for dynamical systems subject to nonholonomic constraints. The geometric formulation of Hamilton-Jacobi theory for such constraints is then developed, following the ideas of separation of variables technique and the canonical transformations. It is shown that the equations of motion which follow from the principle of d’Alembert are identical to the equations which follow from the variational action principle.

Speaker
Biography:

Azrifitria has completed  her  PhD at the Indonesia  University School of Medicine. She is the head of pharmacy department at islamic state University Syarif Hidayatullah Jakarta, Indonesia. She has published several  papers in reputed journals and get  some course at pharmacy field at tokushima bunry japan.  

 

Abstract:

Catha edulis (khat) fresh leaves and tops are chewed or dried and consumed as tea. It is habitually chewed by many peoples in Yemen, East Africa and Indonesia. The abuse of Catha edulis (khat), widely, has been increasing since the mid-2000s. These substances are derivatives of the naturally occurring compound cathinone, which is the primary psychoactive component of khat. There were two types of khat leaves, that called crimson and green khat. The difference found in the branches which crimson khat had twigs maroon red and the green khat had  brownish green. Viewing of cathinone and cathine levels used GC-MS because the components can be analyzed and characterized by exploiting the properties of their volatility. The efficiency for the extraction and isolation of cathinone and cathine  were investigated. GC-MS chromatogram shown  a cathinone content on green khat  had a peak high 213,800, while the crimson khat had peak high 111,693 which means green khat contains more cathinone that had a retention time of about 22.3 minutes. The Chatine level on green and crimson khat was very low that had a retention time of about 22.7 minutes. The minimum effective concentration  of the green and crimson khat khat extract  to totally immobilise sperm within 20 seconds was 200 mg/ml.  This Study shown that the  extract of Catha edulis  possesses spermicidal activity and cathinone level  at a green khat more high than a crimson khat.

Bogdan Florin Craciun

Center of Advanced Research in Bionanoconjugates and Biopolymers, Romania

Title: Self-assembled polymeric vectors for gene delivery
Speaker
Biography:

Bogdan Florin Craciun has obtained master degree at age 24 at Faculty of Chemistry, “Alexandru Ioan Cuza” University, Iasi, being specialized in organic chemistry. His work during master is highlighted by being co-author in three published papers, two of them represent the work accomplished in a practical stage made in Germany. Currently he is in first year of PhD at Petru Poni Institute of Macromolecular Chemistry, researching the field of drug delivering systems.

Abstract:

In recent decades a considerable attention was accorded to the field of drug delivery. A fraction of this domain is based on polymeric micelles with nanometer dimensions which proved their efficiency in vitro and in vivo testing. In this context, a library of self-assembled vectors based on squalene, benzene-1,3,5-tricarboxaldehyde (TA), branched polyethylenimine (PEI) and linear polyethylene glycol (PEG), was obtained as vectors for gene delivery. We have shown that this type of polymeric vectors possess a great affinity for binding the nucleic acid and good transfection efficiency on HeLa cell line. The main objective of the presented work was to find the best transfecting vector by tuning the ratios of components in the system, thus maximizing the transfection efficiency keeping a minimum grade of toxicity. We applied dynamic combinatorial chemistry for the preparation of vectors and it was proved the formation of polyplexes by gel electrophoresis and TEM. In vitro biological assessments show that the content of PEG in obtained polyplexes, plays a crucial role in transfection efficiency and cytotoxicity on HeLa cell line.

Speaker
Biography:

Abstract:

In this article, dynamic interactions among stock return, Research and Development (R&D) investment, patent applications and patent propensity of firms are studied. Patent innovation leader and follower firms are identified with respect to their quality-adjusted knowledge stock. Significant and positive dynamic spillover effects are obtained in a panel vector autoregressive model. We find positive dynamic spillover effects from patent innovation leader to followers. We show that an increasing degree of competition enhances innovation and patent applications, which helps firms appropriating part of the benefits of their
R&D investments.

Speaker
Biography:

Zeeshan completed his undergraduate and PhD (2007) from Queen Mary, University of London. He further conducted post-doctoral studies from Queen Mary and University College London for 6 years before taking up his first academic post as a Lecturer. Zeeshan is a full Professor and he is the EPSRC EHDA Network lead in the UK (a highly interdisciplinary initiative between academia and industry focusing on the development novel advanced drug delivery systems engineering). He is also a Royal Society Industry Fellow. He has published extensively in the area and his research group focuses on the development of novel drug delivery systems and their engineering platforms. He is on the editorial board for various notable journals and peer reviews for all major pharmaceutical and biomaterial journals.

 

Abstract:

Encapsulation is a crucial strategy in several aspects of Pharmaceutical development. This can be approached from both material and processing aspects and lends to controlled release, material safeguarding and providing several engineering benefits. This talk will look at encapsulation technologies from a processing perspective; specifically focusing on electrical encapsulation methods. An overview of the underlying process will be provided and examples of how such principles can be modulated to match emerging technologies (e.g. nanoparticles, 3D printing fibrous delivery systems) will be shown. Furthermore, the talk will also discuss briefly developments in the field and the emerging roles of industry for such technologies.

Speaker
Biography:

Abstract:

This work studies the antifungal capacity of the essential oil of spontaneous aromatic plant with vocation medicinal used in the traditional treatments in the South-West of Algeria: Artemisia campestris L. The local plant tested gives a good essential oil yield (0.37%). The physico-chemical analysis of the essential oil of this plant specie has enables to us to even characterize to identify our oil.  Antifungal activity of the essential oil was studied witch respect to seven fungal strains with various concentrations. The results of direct contact method show that the oil of Artemisia campestris L. is proven very effective on the mycelial growth of the moulds. All strains were inhibited at concentration as weak as 1/70 (v/v), Fusarium oxysporum f.sp. albedinis and Penicilluim expansum were most sensitive, being inhibited as from 1/800 (v/v) and 1/500 (v/v) respectively. This essential oil has a fungistatic effect. In addition to the growth of the mycelium, the essential oil of plant showed, in vitro, a antifungal activity at least important on the two other developmental stages, germination and the sporulation, of all fungi . All strains were inhibited at concentration as weak as 1/100 (v/v). Fusarium oxysporum f.sp. albedinis was most sensitive, being inhibited as from 1/1500 (v/v).