Novel amine-functionalized benzimidazolium salts: Synthesis, characterization, bioactivity, and molecular docking studies

A series of amine-tethered benzimidazolium salts were synthesized by the reactions between 1-(1-methyl-2-dimethylaminoethyl)benzimidazole and various alkyl halides. The characterization of the newly synthesized salts was done by spectroscopic methods. Also, 2e, 2f, and 2h have been docked into the catalytic active site hCA I, hCA II, AChE, BChE, and alpha-glycosidase enzymes. We have identified high binding affinity and explained inhibition mechanism of the compounds against the enzymes. These novel amine-functionalized benzimidazolium salts derivatives were good inhibitor compounds of the aglycosidase, hCA I and II isoforms, and both cholinesterase enzymes with K-i values in the range of 0.63 +/- 0.05-3.63 +/- 0.83 nM for a-glycosidase, 8.42 +/- 1.03-27.04 +/- 3.74 nM for hCA I, 7.94 +/- 0.74 - 21.82 +/- 5.81 nM for hCA II, 136.38 +/- 19.55-247.34 +/- 34.06 nM for BChE, and 124.24 +/- 13.94 - 283.55 +/- 54.06 nM for AChE, respectively. Among the inhibitors, 2e, 2e, 2f, 2f, and 2h were obtained to be the excellent inhibitors with Ki values of 8.42 +/- 1.03, 7.94 +/- 0.74,124.24 +/- 13.94,136.38 +/- 19.55, and 0.63 +/- 0.05 nM for hCA I, hCA II, AChE, BChE, alpha-glycosidase enzymes, respectively. The ability to model some metabolic enzymes receptors and theirs inhibitors in silico are important because they can save valuable resources and help to rationalize the mode of binding, and to design better inhibitors. (C) 2020 Elsevier B.V. All rights reserved.