Synthesis and anti-Alzheimer activity of new N-(5, 6-dimethyl-1H-benzo[d] imidazol-2-yl)-1-phenylmethanimine derivatives

Abstract

The cholinesterase group, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), is responsible for inhibiting the actions of choline esters. Benzimidazole derivatives, renowned for their aromatic organic heterocyclic structure, exhibit diverse biological activities, including enzyme inhibitory effects. Imine compounds, easily synthesized, demonstrate notable biological efficacy against various pathogens and enzymes. Synthesize, purify, and characterize novel benzimidazole scaffolds, and evaluate their anti-Alzheimer’s activity by measuring AChE and BChE activities. A new series of benzimidazole phenylmethanimine derivatives (3a–3d) was synthesized through refluxing amine with various benzaldehydes. Products underwent purification by solvent washing and characterization using spectroscopic methods. In vitro anti-Alzheimer’s activity was assessed by measuring inhibitory activity (half-maximal inhibitory concentration [IC50]) against cholinesterase enzymes. the newly synthesized Schiff bases, purified solely by solvent washing, yielded high percentages (81%–91%). These derivatives showed significant inhibitory activity, with low IC50 values observed for compounds 3a and 3d against both enzymes. Molecular docking studies estimated binding energies and identified interacting amino acids in active pockets. Four new derivatives were synthesized with high yields using the classical reflux method. Purification involved solvent washing only, followed by direct spectroscopic analysis. In vitro inhibitory activities against AChE and BChE enzymes were observed, with compounds 3a and 3d showing promising results. Docking studies revealed higher inhibitory activity and lower IC50 values for two derivatives, indicating their potential as potent inhibitors.

Keywords

• acetylcholinesterase; alzheimer; butyrylcholinesterase; benzimidazole; molecular docking