Design, Synthesis, Characterization and Preliminary Evaluation of New 1H-benzo[d]imidazole-1yl-derivatives as Acetylcholine Esterase Inhibitors

Abstract

Background: Alzheimer disease (AD) is the most common type of dementia, which is still a problem that everyone must deal with. In a continuous effort to find effective treatments, the new candidates for AD therapy have the capacity to scavenge excessive levels of free radicals and inhibit acetylcholinesterase (AChE). Objectives: This study focuses on synthesizing and biologically evaluating novel hybrid compounds (1-3) as acetylcholine esterase inhibitors. Methods: The benzimidazole has been added and then coupled with coumaric acid, cinnamic acid, and lipoic acid as conjugates, which are expected to have dual action as acetylcholinesterase inhibitors and antioxidants. The synthesis of benzimidazole derivatives (1-3) was accomplished and then characterized using 1H-NMR and elemental analysis. Additionally, their characteristics were assessed in vitro against the AChE enzyme. Results: The new compounds produced a potent inhibitory activity that may serve as a lead molecule for the synthesis of novel anti-AD molecules. Compound-1 has an inhibition percentage that is close to that of the authorized medication galantamine (95.386%), whereas compound-3 has the lowest inhibition percentage (88.647%). Conclusions: A very good yield was achieved during the synthesis of the benzimidazole derivatives (1-3) from the starting material. They can serve as potential candidates for acetylcholine esterase inhibitors.