Benzimidazolium Salts Containing Trifluoromethoxybenzyl: Synthesis, Characterization, Crystal Structure, Molecular Docking Studies and Enzymes Inhibitory Properties

The method for producing 4‐trifluoromethoxybenzyl substituted benzimidazolium salts is described in this article. The method is based on the reaction of 4‐trifluoromethoxybenzyl substituent alkylating agent with 1‐alkylbenzimidazole. This method yielded 1‐(4‐trifluoromethoxybenzyl)‐3‐alkylbenzimidazolium bromide salts. These benzimidazolium salts were characterized by using 1H‐NMR, 13C‐NMR, FT‐IR spectroscopy, and elemental analysis techniques. The crystal structure of 1f was enlightened by single crystal X‐ray diffraction studies. Also, the enzyme inhibition effects of the synthesised compounds were investigated. They demonstrated highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (Ki values are in the range of 7.24±0.99 to 39.12±5.66 nM, 5.57±0.96 to 43.07±11.76 nM, and 4.38±0.43 to 18.68±3.60 nM for AChE, hCA I, and hCA II, respectively). In molecular docking study, the interactions of active compounds showing activity against AChE and hCAs enzymes were examined. The most active compound 1f has −10.90 kcal/mol binding energy value against AChE enzyme, and the potential structure compound 1e, which has activity against hCA I and hCA II enzymes, was −7.51 and −8.93 kcal/mol, respectively.