Pharmaceutical Chemistry

Biography

Biography: Sartaj Tabassum

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