Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

Development of Multi-Target Directed Ligands (MTDLs) has emerged as a promising approach for targeting complex etiology of Alzheimer’s disease (AD). Following this approach, a new series of 2-phenyl-1-benzopyran-4-one derivatives were designed, synthesized and biologically evaluated as inhibitors of acetylcholinesterases (AChEs), advanced glycation end products formation (AGEs) and also for their radical scavenging activity. The in vitro studies showed that the majority of synthesized derivatives inhibited acetylcholinesterase (AChE) with IC50 values in the low-micromolar range. Among them, inhibitors 7h, 7k and 7a, strongly inhibited AChE, with IC50 value of 6.33, 7.56 and 11.0 nM, respectively, and were more potent than the reference compound donepezil. Moreover, the molecular docking study displayed that most potent compounds simultaneously bind to catalytic active site and peripheral anionic site of AChE. Besides, these compounds also exhibited greater ability to inhibit advanced glycation end products formation with additional radical scavenging property. Thus, 2-phenyl-1- benzopyran-4-one derivatives might be the promising lead compound as potential poly-functional anti-Alzheimer’s agents.

Biography

Email: manjinder2007@gmail.com