Synthesis, in silico studies and cytotoxicity evaluation of novel 1,3,4-oxadiazole derivatives designed as potential mPGES-1 inhibitors

Year 2020, Volume: 24 Issue: 4, 436 - 451, 27.06.2025

Gizem Erensoy Kai Ding Chang-guo Zhan Ammar Elmezayen Kemal Yelekçi , Merve Duracik Özlem Bingöl Özakpınar , İlkay Küçükgüzel

https://doi.org/10.35333/jrp.2020.187

Abstract

A series of new 1,3,4-oxadizole derivatives containing thioether group, has been synthesized to investigate their mPGES-1 inhibitory activities. The synthesized compounds were also evaluated for their anticancer and COX-1/2 inhibitory activities. All compounds were checked for their purity using TLC and HPLC analyses. The melting points, elemental analysis, FT-IR, 1H-/13C-NMR and LR-MS data were utilized for structural characterization. The most potent derivative was 2-[5-{[2-methyl-5-(propan-2-yl)phenoxy]methyl}-1,3,4-oxadiazol-2-yl)sulphanyl]-1- (phenyl)ethan-1-one 3a, which showed inhibitory activity against mPGES-1 with an IC50 of 4.95 μM. Docking studies with mPGES-1 and COX-1/2 enzymes revealed their affinity and potential binding mechanism for the tested compounds.

Keywords

1,3,4-Oxadiazoles , thioethers , mPGES-1 inhibition , COX-1/2 inhibition , anticancer activity , molecular docking , ADME prediction

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