2^nd International Conference on Pharmaceutical Chemistry October 02-04, 2017 Barcelona, Spain

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.³ 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.

Biography:

Mauro Safir Filho has a degree in Industrial Chemistry and a master’s degree in Chemistry from the Federal University of Rio Grande do Sul (UFRGS), Brazil. Now he is PhD student at University Côte d'Azur, in Nice, France. He has experience in organic synthesis and photochemistry and now has been working on methodologies of post-synthetic modifications of oligonucleotides.     
 

Abstract:

Targeting RNA by using small molecules is one of the most intriguing challenges of current medicinal chemistry because, even if a large number of RNA-binding agents have already been identified, the rational design of synthetic molecules that would be specific for a particular RNA structure remains extremely difficult. Recently, this research field raises to an even greater interest since the discovery of new roles of non-coding RNA molecules, including the regulation of a wide number of biological processes as gene expression, tumorigenese and viral translation in chronic diseases, making them potential and important druggable targets.  In this context, our research group devoted a lot of effort to develop small-sized organic molecule targeting RNAs. Our ligand design consisted in the combination of molecular recognition elements to enhance site specificity with electrostatic interactions to strengthen the complex stability. The preparation of these multimodal ligands was accomplished by assembling artificial nucleobases, able to form triplets through Hoogsteen interactions with A:U and G:C base pairs, with basic amino acid residues. The affinity and specificity of our ligands were evaluated towards the IIId loop of HCV Internal Ribosome Entry Site (IRES) as RNA model. Low micromolar dissociation constants could be obtained for our best ligand with two-fold higher affinity compared with the non-specific RNA binder neomycin used as positive control. Furthermore, high site specificity to target the single U:A base pair besides the bulge was also observed. Moreover, great selectivity to target the HCV IRES IIId loop instead natural tRNA was achieved.

This work is supported by CAPES (fellowship to MSF, process number 99999.0011495/2015-01)

Biography:

Hamid Irannejad has completed his Doctor of Pharmacy at Kerman University of Medical Sciences and PhD at Tehran University of Medical Sciences, Iran. His Postdoctoral studies were accomplished at University of Siena, Italy, under the supervision of Prof. Maurizio Botta. Currently, he is serving as an Assistant Professor at Mazandaran University of Medical Sciences. He has published nearly 20 papers in reputed journals in the field of Medicinal Chemistry.      
 

Abstract:

Alzheimer’s disease is a neuropathologic disorder characterized by intracellular neurofibrillary tangles and amyloid aggregates in the CNS. In recent years numerous approaches have been used to combat AD like small molecule inhibitors of Aβ aggregation, anti-inflammatory agents, cholinesterase, β- and γ-secretase. Herein, we report synthesis of some 5,6-diaryl-1,2,4-triazines 3a-f and 8a-e as potential agents for treatment of AD. We evaluated them against both H₂O₂ and β-amyloid induced toxicity in PC-12 and SH-SY5Y cells and the extent of cell viability and apoptosis were assessed. The synthesis of compounds (3a-f) was started by 1,2-diketones, in which triazine ring closure was performed by thiosemicarbazide and alkylation by ethyl chloroacetate to afford compounds 3a-f. Synthetic route for compounds 8a-e was started by an acylation reaction of anisole with phenylacetic acid derivatives. The oximation in the alpha position of carbonyl group was performed by use of sodium methoxide and butylnitrite. The next two steps, were performed similarly to afford final compounds 8a-e. All compounds showed significant neuroprotective activity with EC₅₀ values ranging from 14-30 µM. Most compounds could increase cell viability compared to amyloid treated group. Surprisingly, 3-thioxo-1,2,4-triazin-2(3H)-yl) acetate derivative 8e was the most potent compound in both tests with EC₅₀ of 14 µM and could increase 40% of cell viability revealed by cytometric analysis with Annexin V/PI staining. It was also shown that 8e has more neuroprotective activity than Quercetin. Morphologic evaluation of cells by DAPI staining and TUNEL assay showed the effectiveness of this compound to improve neurite outgrowth in neuronal cells.

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.

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.

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

Biography:

Abstract:

In the present study, the anti-HIV-1 activity of magnetic water at different intensities of 250, 750, 1000, 2000 gauge has been determined. A time of drug addition assay was done to identify the target of anti-HIV-1 agents. MW at different intensities showed potent anti-HIV-1 activity. EC90 of MW was achieved at intensity of 2000 gauge. The time of drug addition study demonstrated that the inhibitory effect of MW is before HIV-1 infection. The frequency and intensity of CD4, C-C chemokine receptor type 5 (CCR5) and chemokine receptor type 4 (CXCR4) on CD4+ T cells were not changed in cells treated with MW at different intensities. The results demonstrated that MW might be a suitable candidate for in vivo testing of anti-HIV infection.

Biography:

Fatemeh Majidi Arlan was born in Urmia (Iran) in 1984. She received his degree in Pure Chemistry from the Urmia University. She will receive his Ph.D degree in Organic Chemistry from the Urmia University (Iran) in 2017 after completing his research in the Study of Synthesis of chromene and pyridine heterocyclic derivatives by one-pot, multicomponent reaction of aryglyoxals, methylene active compounds and enamines in the presence of nanocatalysts and study of their interactions with heavy metals using analytical techniques under the guidance of Professor Jabbar Khalafy. Her current research interest focus on the Synthesis of new series of pyrazolo[3,4-b][1,6]naphthyridine in presence of nano-Al₂O₃

Abstract:

Pyrazolonaphthyridine is a fused polycyclic heterocycles with four nitrogen-atoms, the pyrazolonaphthyridine derivatives have received much attention in recent years due to their wide biological and pharmacological activities such as potent phosphodiesterase 10A inhibitors [1], selective histamine 4 receptor antagonists [2] bombesin receptor subtype-3 agonists [3] and protein kinase inhibitors [4]. Herein, we report the one-pot threecomponent synthesis of new series of pyrazolo[3,4-b][1,6]naphthyridine in the presence of different catalysts such as L-alanin, p-TSA and nano Al₂O_3.  Ease of   purification of products, isolation of catalysts, using water/ ethanol as a green solvent, high yields and shorter reaction times in presence of nanocatalyst in comparison with other catalysts are the advantages of this procedure. 

Biography:

Arezou Ghahghaei completed her PhD from University of Australia (Wollongong). She is Biochemist, Associated Professor and Head of Department of Biology. Her research focuses on pharmaceutics effect on protein aggregation. She has published several papers in reputed journals.

Abstract:

The formation and deposition of protein fibrillar aggregates in the tissues is associated with several neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Nanoparticles possess an enormous surface area and are found to inhibit protein amyloid formation. Recently plant-mediated nanoparticles synthesis has drawn a great deal of attention because it is rapid, environmentally friendly, cost effective and it provides a single step technique for the biosynthetic processes and is safe for human therapeutic use. The aim of this study was to assess the effect of green synthesis AgNPs from Pulicaria undulata L. on the reduction of protein aggregation in reduced α-lactalbumin. The results showed that green synthesis AuNPs have the ability to prevent the aggregation of α-lactalbumin in a concentration-dependent manner. This inhibitory effect of AuNPs probably caused by decreasing the rate of fibrillation through surface absorbing of free monomeric peptides and prevent amyloid fibril formation. In fact, by increasing the concentration of AuNPs within a specified range, the adsorption and interaction between AuNPs and protein have increased and protein conformational changes and self-association decreased, thus amyloid aggregation is prevented. In the main, results of this study show that green AuNPs mediated by Pulicaria undulata L. has the capability in inhibiting amyloid fibril formation and can be used as a therapeutic approach in the treatment of amyloid disease such as Alzheimer disease. 

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.

Biography:

Fabio Luiz Paranhos Costa has completed his PhD from University Federal of Rio de Janeiro and Postdoctoral studies from Univesity Federal Fluminense. He has published more than 20 papers in reputed journals.

Abstract:

In this work, we present a new GIAO-HDFT universal scaling factor (mPW1PW91/3-21G//PM7(I)) and a comparative study in which is investigated its ability to predict NMR 13C chemical shifts (δ) with high cost-effectiveness ratio. A set of 22 small molecules providing 27 different 13C δ determined in the gas phase was used for all scaling factors protocols: B3PW91/ccpVDZ//B3PW91/cc-pVDZ (II), B3PW91/cc-pVTZ//B3PW91/cc-pVDZ (III), B3LYP/6-311+(2d,p)//B3LYP/6-31G(d) (IV), mPW1PW91/6-31G(d)//PM7(V) , mPW1PW91/6-31G(d)//mPW1PW91/6-31G(d) (VI). Despite the calculation approximations the δ calculated at the GIAO-mPW1PW91/3-21G//PM7 using a simple relationship (δscal = 1.14. δcalc – 4.7, where δcalc and δscal are the calculated and the linearly scaled values of the 13C δ, respectively) were able to yield MAD and RMS errors as small as those obtained with other GIAO-HDFT with bigger basis sets (protocols (II) to (VI)). The robustness of the new protocol and its applicability to practical problems was evaluated by the calculation of the δ for two natural compounds with synthesis, biological and therapeutic interest: tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione) and (-)- loliolide (7aR)-6-hydroxy-4,4,7a-trimethyl-6,7-dihydro-5H-1-benzofuran-2-one. For both compound, the 6 protocols presented good agreement with experimental data. Moreover, for the second compound, the new protocol performs even better than the 5 others. In conclusion, GIAOmPW1PW91/3-21G//PM7 linear regression obtained by using the experimental and the calculated data, is a very attractive tool as an alternative to more computationally demanding approaches, which are usually applied in order to achieve 13C NMR δ calculations.