Pervaiz_2020_Chem.Biodivers__

The catalytic potential of pyridine-2-carboxlic acid has been evaluated for efficient, green and solvent free synthesis of 2,4,5-trisubstituted imidazole derivatives. The compounds were synthesized by condensation reaction of substituted aromatic aldehydes, benzil and ammonium acetate ( 3a-3m ) in one pot in a good to excellent yield (74-96 %). These compounds were evaluated against acetylcholinesterase (AChE) enzyme activity to explore their potential against Alzheimer's disease. Among this series of compounds 3m bearing one ethoxy and a hydroxyl group on the phenyl ring on 2,4,5-trisubstituted imidazoles proved potent AChE inhibitor (102.56+/-0.14). Structure-activity relationship (SAR) of these compounds was developed. Molecular dockings were carried out for the inhibitors 3m , 3e , 3k , 3c , 3a , 3d , 3j , and 3f in order to further investigate the binding mechanism. The inhibitor molecule was molecularly docked with acetylcholinesterase to further study its binding mechanism. The amino group of the inhibitor 3m forms an H bond with the oxygen atom of the residue (i.e., THR121), and has a bond length of 3.051 A.