Novel thiadiazol derivatives; design, synthesis, biological activity, molecular docking and molecular dynamics

Abstract

Currently, selective COX-2 inhibitors are used as a novel alternative approach in the course of pain man-agement due to their reduced adverse that generally occur after COX-1 inhibition by non-selective COX inhibitors. In this work, 16 new thiadiazole derivatives ( 3a-3p ) were designed, synthesized and biolog-ically evaluated for their COX-1 and COX-2 inhibitory potential using the in vitro fluorometric method. The biological evaluation showed that compounds 3c and 3d displayed significant activity against COX-2 with IC50 values of 0.350 +/- 0.015 mu M and 0.134 +/- 0.004 mu M, respectively, making the compound 3d similar in its activity to the reference drug celecoxib (IC50 = 0.132 +/- 0.005 mu M). Further docking simulation also re-vealed that the most active derivative ( 3d ) interacted with the enzyme active site in a similar manner to celecoxib. The binding modes of the compound on COX-2 were fully elucidated by molecular dynamics studies. (c) 2022 Elsevier B.V. All rights reserved.