Synthesis and docking studies of novel benzimidazole derivatives containing thiophene and triazole rings as potential urease inhibitors

Abstract

Abstract: A new series of 5,6-dichloro-benzimidazoles containing thiophene ring derivatives of thiosemicarbazides and triazoles were designed, synthesized and characterized by spectral methods like as IR, 1H-NMR, 13C-NMR and elemental analysis. The compounds antiurease activity studies have done according to VanSlyke method and IC values were calculated in μM unit. All newly synthesized compounds containing thiophene ring showed urease inhibitory activity with IC50 values between 1.52 and 0.07 µM. 5-{[5,6-Dichloro-1-(2-thienylmethyl)-1H-benzimidazol-2-yl]methyl}-4-methyl-4H-1,2,4-triazol-3-thiol (Va) proved to be the most potent enzyme inhibition activity with IC50 = 0.07 ± 0.008 μM. Especially compounds (Va–f) have best results with triazole ring. All synthesized compounds were docked at the active sites of the Jack bean urease enzyme to investigate the reason of the inhibitory activity and the possible binding interactions of enzyme-ligand complexes. 2-{[5,6-Dichloro-2-(2-thienylmethyl)-1H-benzimidazol-1-yl]acetyl}-N-(4-clorophenyl)hydrazine carbothioamide (IVe), which has the second highest in vitro urease inhibitory activity with an IC50 of 0.11 μM compared to other compounds, has the highest binding energy of –8.97 kcal/mol.