Influence of Chirality of Benzimidazole Amine Hybrids on Inhibition of Human Erythrocytes Carbonic Anhydrase I, II and Acetylcholinesterase.

Novel chiral benzimidazole amine hybrids (4a-4d) were synthesized from commercially available amine [(R)- (+)-phenylethylamine, (-) (S)-(-)-phenylethylamine, (-) (R)-(-)-cyclohexylethylamine, (S)-(+)-cyclohexylethylamine] and 2-(chloromethyl)-N-tosyl-1H-benzimidazole. The synthesized compounds (4a-4d) were characterized by IR, NMR, and LC/MS analysis. The inhibitory effect of 4a-4d on human erythrocytes carbonic anhydrase I (hCA-I), II (hCA-II), and acetylcholinesterase (AChE) activity was investigated. For hCA-I, the IC50 values of 4a-4d were found to be 4.895 μM, 1.750 μM, 0.173 μM, and 0.620 μM, respectively, and for hCA-II, the IC50 values of 4a-4d were found to be 0.469 μM, 0.380 μM, 0.233 μM, 0.635 μM, respectively. Furthermore, IC50 values of 4a-4d on AChE were found as 87.5 nM, 100 nM, 26.92 nM, and 100 nM, respectively. In addition, molecular docking analysis was performed to evaluate the affinity of 4a-4d against hCA-I, hCA-II, and AChE and explain their binding interactions.