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

Abstract

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 1alkylbenzimidazole. This method yielded 1-(4-trifluoromethoxybenzyl)-3-alkylbenzimidazolium bromide salts. These benzimidazolium salts were characterized by using 1 H-NMR, 13 C-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) (K i 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 À 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 À 7.51 and À 8.93 kcal/mol, respectively.

Benzimidazolium Salts Bearing Nitrile Moieties: Synthesis, Enzyme Inhibition Profiling, and Molecular Docking Analysis for Carbonic Anhydrase and Acetylcholinesterase

“…K i values are in the range of 7.24 to 39.12 nM, 5.57 to 43.07 nM, and 4.38 to 18.68 nM for AChE, hCA I, and hCA II. When we compared the results of trifluoromethoxybenzyl groups with the nitrile groups in our study, trifluoromethoxybenzyl groups exhibited more effective inhibition [72] . In another study, Tezcan and her colleagues examined the effect of trifluoromethyl‐bonded Benzimidazolium salts on the AChE enzyme and found the best effect in the 1,3‐di(3‐trifluoromethylbenzyl)benzimidazolium bromide compound (K i : 1.36±0.34 μM).…”

“…When we compared the results of trifluorometh- oxybenzyl groups with the nitrile groups in our study, trifluoromethoxybenzyl groups exhibited more effective inhibition. [72] In another study, Tezcan and her colleagues examined the effect of trifluoromethyl-bonded Benzimidazolium salts on the AChE enzyme and found the best effect in the 1,3-di(3-trifluoromethylbenzyl)benzimidazolium bromide compound (K i : 1.36 � 0.34 μM). Compared to the results in our study, AChE enzyme inhibition by trifluoromethoxybenzyl groups was more effective than this study reported in the literatüre.…”

Synthesis, Theoretical, in Silico and in Vitro Biological Evaluation Studies of New Thiosemicarbazones as Enzyme Inhibitors

“…[25] They also found clinical relevance as antiobesity, antiglaucoma drugs, diuretics, antitumor, and antiepileptics agents. [26] A cholinergic enzyme called acetylcholinesterase (AChE) is mainly present in postsynaptic neuromuscular junctions, especially in nerves and muscles. A natural neurotransmitter called acetylcholine (ACh) is quickly degraded into acetic acid and choline.…”

“…In particular, CA inhibitors (CAIs) emerged as useful tools in diseases typically not associated with this class of pharmacological agents, such as oxidative stress, as an anti‐infective agent, Alzheimer's disease (AD), neuropathic pain, cerebral ischaemia, and rheumatoid arthritis in the last decades [25] . They also found clinical relevance as antiobesity, antiglaucoma drugs, diuretics, antitumor, and antiepileptics agents [26] …”