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, cilt.7, sa.28, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 7 Sayı: 28
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/slct.202201548
  • Dergi Adı: CHEMISTRYSELECT
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Anahtar Kelimeler: Benzimidazole, oxadiazole, anti-inflammatory, molecular docking, dynamics simulations
  • Erciyes Üniversitesi Adresli: Evet

Özet

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.