Design, Synthesis, in Vitro and in Silico Studies of Benzimidazole-Linked Oxadiazole Derivatives as Anti-inflammatory Agents


ÇELİK İ. , YILMAZ SARIALTIN S., ÇOBAN T., KILCIGİL G.

CHEMISTRYSELECT, vol.7, no.28, 2022 (Journal Indexed in SCI) identifier

  • Publication Type: Article / Article
  • Volume: 7 Issue: 28
  • Publication Date: 2022
  • Doi Number: 10.1002/slct.202201548
  • Title of Journal : CHEMISTRYSELECT
  • Keywords: Benzimidazole, oxadiazole, anti-inflammatory, molecular docking, dynamics simulations

Abstract

In this study, 24 new benzimidazole-oxadiazole hybrids were designed and synthesized as anti-inflammatory agents. It was measured their stabilizing potentials against heat-induced human erythrocyte membrane hemolysis for anti-inflammatory activity. Compound 5 w bearing cyclohexyl as R-2 group at the 2(nd) position of oxadiazole ring and 3,4-dimethoxy phenyl at the 2(nd) position of benzimidazole showed the highest membrane stabilizing activity with IC50= 0.50 mM. Antioxidant activity screening of compounds synthesized by ABTS and DPPH radical scavenging assay methods was performed. Molecular docking studies of all compounds were performed against COX-1 and COX-2 with Glide XP. Moreover, to examine the protein-ligand stability of the most active compound 5 w, molecular dynamics simulations of 100 ns duration were performed with COX-1 and COX-2 using Gromacs.