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

• Published in: ChemistrySelect (Weinheim) Vol. 7; no. 28
• Main Authors: Celik, Ismail, Sarıaltın, Sezen Yılmaz, Çoban, Tülay, Kılcıgil, Gülgün
• Format: Journal Article
• Language: English
• Published: 27.07.2022
• Subjects: anti-inflammatory; Benzimidazole; dynamics simulations; molecular docking; oxadiazole
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202201548

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 R2 group at the 2nd position of oxadiazole ring and 3,4‐dimethoxy phenyl at the 2nd 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. The compound 5 w (IC50: 0.5 mM) showed promising anti‐inflammatory activity when compared to the reference compound indomethacin (IC50: 4.44 mM). On the other hand, they did not produce good antioxidant activity. According to the molecular docking study, compound 5w has the inhibitory property of both cyclooxygenase‐1 and −2.