Synthesis and Molecular docking Investigations of Ring-Fused Benzimidazoles as Novel Acetylcholinsterase Inhibitors

Abstract

Alzheimer’s disease (AD) is a highly neurodegenerative brain disease and is the most prevalent type of dementia. AD affects parts of brain that are responsible for memory, language and thought. Cholinergic hypothesis proposed that deficiency of acetylcholine in certain zones of brain may be responsible for the progressive memory deterioration observed in patient with AD. Therefore, inhibition of acetylcholinesterase (AChE) may represent a hopeful target for treatment of AD. Herein, new series of ring-fused benzimidazoles (benzoimidazo[1,2-c] quinazoline derivatives (scheme 1, compounds 2a-d) and benzoimidazo[2,1-c] triazole derivatives (scheme 2, compounds 7 and 8a-b) as main scaffolds) were synthesized using benzene1,2-diamine as a starting material and characterized by mass spectroscopy, IR, H1NMR, C13 NMR and elemental analysis. Afterward, molecular docking studies were carried out on AChE and demonstrated the preferential binding interaction of synthesized compounds with AChE binding site. Therefore, the obtained results imply that ring-fused benzimidazoles may act as an auspicious lead compounds for further optimization and biological evaluation against AChE.