Design , Molecular Modeling and Grinding Preparation of Some Isoxazole Derivatives as COX2 Inhibitors

Abstract

In this work 42 compounds of isoxazole derivatives were designed using ACD/Chemical Sketch Software and predicted their anticancer activity IC50 inhibition of the half concentration of the cancer cells. Prediction results showed that most of these compounds more effective by IC5o values lower than the reference standard (Indomethacin) for inhibition IC50=7.36μM, All the compounds were examined to be docked into the inhibitor site of protein by using MOE software. Among these derivatives 19 compounds showed more than two interactions with receptor COX-2 with binding energy less than -20 kcal/mol. Isoxazoles derivatives acts as potent COX-2 inhibitors hence, in the present study isoxazole is synthesized in order to obtain new compounds with anticancer activity. Due to quantitative structure activity relationship and molecular docking eleven new substituted isoxazole derivatives which have IC50 more and less than the standard reference lower binding energy were prepared by cyclocondensation through grinding chalcones derivatives with hydroxyl amine hydrochloride and soild sodium hydroxide in equiamolar quantity in mortar and pestle as known grinding stone method (solvent free), the amino group in hydroxyl amine attack the beta-position of enones to give isoxazoles. The synthesized compounds were characterized by M.P , TLC, UV, IR.