Bisbenzimidazole salts and their in silico-in vitro inhibitory abilities on hCAI, hCAII, and AChE enzymes

Abstract

Abstract New eight bisbenzimidazolium halides were prepared from alkyl halides and 4,4'-bis((benzimidazol-1-yl)methyl)-1,1'-biphenyl. The structures of benzimidazolyum salts were identified thanks to spectroscopic methods. Inhibitory activities of benzimidazole derivatives were measured against hCA I, hCA II and AChE enzymes. It was observed that all benzimidazolium halides have good inhibitory activities against enzymes. They showed highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (Ki values are in the range of 15.66 ± 0.87 to 49.71 ± 10.11 nM, 14.62 ± 1.51 to 70.68 ± 2.67 nM, and 17.38 ± 2.81 to 37.94 ± 10.09nM for AChE, hCA I, and hCA II, respectively). The binding orientation of the synthesized bisbenzimidazole salts was evaluated by molecular docking studies, reflecting the importance of the p-methylbenzyl, m-methylbenzyl, p-nitrophenethyl and 3-(1,3-dioxoisoindolin-2-yl)methyl) groups in protein-ligand interaction. The docking results support the Ki values of the respective compounds in this study. Their interactions with the mentioned enzymes clearly demonstrate the structure-activity relationships against the different targets in three dimensions at atomic level.