Novel aryl(4-phenylpiperazin-1-yl)methanethione derivatives as new anti-Alzheimer agents: Design, synthesis, in vitro and in silico assays

Abstract

In this work, a new series of aryl(4-phenylpiperazin-1-yl)methanethione derivatives 4a-n was designed, synthesized, and evaluated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha glucosidase. Most of the synthesized derivatives were more potent than standard inhibitor donepezil against AChE and all the synthesized compounds were more potent than donepezil against BChE. Moreover, some of these new compounds were more potent than acarbose (positive control) against alpha glucosidase. The obtained results revealed that (3-chlorophenyl)(4-phenylpiperazin-1-yl)methanethione 4k and was the most potent compound against cholinesterase enzymes (AChE and BChE). Docking study of compound 4k in the active site of cholinesterase enzymes showed that this compound established important interactions with the main residues of the target enzymes. Druglikeness/ADME/Toxicity profile prediction of the most potent compounds also demonstrated that these compounds can be drug candidates and have the appropriate properties in terms of ADME and Toxicity. (c) 2022 Elsevier B.V. All rights reserved.