Rationally Designing and Eco-Friendly Synthesis Pi-Class of Glutathione-S-Transferase as Candidate Inhibitors
Abstract
. Computer aided drug design has become an important part of modern rational drug design,\r\nthe advances in X-ray crystallography together with modern approaches of drug design helps the researchers to work at molecular level. Therefore, the malignant tumor is no more treated like a gross mass\r\nbut it\'s more likely treated on the basis of the molecular differences between normal and cancerous cells.\r\nTo selectively target pi-class of glutathione-S-transferase that\'s over expressed in cancer cells and has a\r\ngreat role in tumor survival and progression, and acts as a housekeeper protein. Three series of compounds were designed starting from 1,3,4-oxadiazole-2-thiol as pharmacophore. In each series optimization was applied to get the best ligand, and docking experiment was conducted by using Auto Dock vina.\r\nThe compounds that were chosen on the basis of docking solutions were successfully synthesized. Ecofriendly reagents like hydrogen peroxide and traces of iodine were used to obtain disulfide bonded bis1,3, 4-oxadiazole and they are compounds 19, 23, 24, 25 and 29. The rationally designed and synthesized\r\ncompounds had lowest dock score. The synthesized compounds were characterized by their physical\r\nproperties and1H-NMR, 13C-NMR and micro elemental analysis which revealed pure and come in consistence with their chemical structures. Rational drug design enabled us to obtain compounds that act as\r\npi-class of glutathione-S-transferase inhibitors. The compounds obtained in this study were in high percentage of yield, generated over a short period of time (30 min) and considered as pure after being characterized by 1H-NMR, 13C-NMR and micro elemental analysis.
Author
Nohad A. AL OMARI1,*, Bnar J. MUHAMMED2 & Hersh N. BAHAULDIN2
ISSN
ISSN 0326 2383 (printed ed.) ISSN 2362-3853 (on line ed.)
Publish Date: 2021-04-21