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


Erensoy G., Ding K., Zhan C., Elmezayen A., Yelekci K., Duracik M., ...More

Journal of Research in Pharmacy, vol.24, no.4, pp.436-451, 2020 (Refereed Journals of Other Institutions) identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 4
  • Publication Date: 2020
  • Doi Number: 10.35333/jrp.2020.187
  • Title of Journal : Journal of Research in Pharmacy
  • Page Numbers: pp.436-451
  • Keywords: 1,3,4-Oxadiazoles, thioethers, mPGES-1 inhibition, COX-1/2 inhibition, anticancer activity, molecular docking, ADME prediction, PROSTAGLANDIN-E SYNTHASE-1, 5-MEMBERED HETEROCYCLIC THIONES, BIOLOGICAL EVALUATION, MOLECULAR DOCKING, ESSENTIAL OIL, CARVACROL, COX-2, CYCLOOXYGENASE-2, IDENTIFICATION, BIOSYNTHESIS

Abstract

© 2020 Marmara University Press.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.