Synthesis, and in vitro biological evaluations of novel naphthoquinone conjugated to aryl triazole acetamide derivatives as potential anti-Alzheimer agents

Abstract

Alzheimer's disease is a neurodegenerative disorder that deteriorates mental ability. Two main cholinesterases named, acetylcholinesterase and butyrylcholinesterase are potential targets against Alzheimer's disease. Cholinesterase inhibitors have beneficial effects to increase brain acetylcholine amounts resulting in neurocognitive function. In the present article, fifteen small molecules of 1, 4-naphthoquinone conjugated to aryl triazole acetamide derivatives were rationally designed, synthesized, and evaluated for their anti-ChE activities followed by molecular docking assessments. Among synthesized derivatives, 7b bearing ortho-chlorine moiety was the strongest inhibitor of acetylcholinesterase and butyrylcholinesterase with K-i values of 10.16 and 8.04 nM respectively compared to the Tacrine as a positive control with K-i = 70.61 and 64.18 nM. Docking studies confirmed the complete fitting of the 7b into the active sites of both enzymes. (c) 2021 Elsevier B.V. All rights reserved.