MOLECULAR MODELLING STUDIES AND SYNTHESIS OF SOME BENZIMIDAZOLE DERIVATIVES AS ANGIOTENSIN CONVERTING ENZYME INHIBITORS

The purpose of this study was to provide some benzimidazole derivatives as angiotensin converting enzyme (ACE) inhibitor. Based on the literature, a total of 19 benzimidazole derivatives were selected for molecular modelling study using the Autodock Vina software. The molecular modelling revealed that compound 10, 16, and 18 had binding affinity with the ACE enzyme closer to the binding affinity of lisinopril. To obtain the compounds 10, 16 and 18, the 2-(butylsulfanyl)-1H-benzimidazole was treated with 2-fluorophenacylbromide, 2-methylphenacylbromide, and 3-nitrophenacylbromide, respectively. The structures of these compounds were confirmed on the basis of their spectral data (IR, 1H-NMR, and 13C-NMR). The synthesized compounds were subjected for their in vitro ACE inhibitory assay using Dojindo ACE Kit-WST test kit, Dojindo Laboratories, Kumamoto, Japan. It was observed that the compounds 10 and 16 had IC50 values less than the standard drug Lisinopril and have the required attributes to become potential candidates as an ACE inhibitor. However, further studies are recommended to ensure their efficacy and safety in different animal models. Key Words: Molecular modelling, Autodock Vina, Synthesis, Benzimidazole derivatives, ACE inhibitors.