Synthesis, biological evaluation, and molecular docking of N'-(Aryl/alkylsulfonyl)-1-(phenylsulfonyl) piperidine-4-carbohydrazide derivatives

Authors: HIRA KHALID, AZIZ UR REHMAN, MUHAMMAD ATHAR ABBASI, RASHAD HUSSAIN, KHALID MOHAMMAD KHAN, MUHAMMAD ASHRAF, SYEDA ABIDA EJAZ, MUHAMMAD QAISER FATMI

Abstract: A series of new N'-[(alkyl/aryl)sulfonyl]-1-(phenylsulfonyl)piperidine-4-carbohydrazide derivatives were synthesized. Starting from ethyl piperidine-4-carboxylate (a), first ethyl 1-(phenylsulfonyl)piperidine-4-carboxylate (1), second 1-(phenylsulfonyl)piperidine-4-carbohydrazide (2), and finally N'-[(alkyl/aryl)sulfonyl]-1-(phenylsulfonyl)piperidine-4-carbohydrazides (4a--n) were synthesized by reacting 2 with alkyl/aryl sulfonyl chlorides (3a--n). The structures of the synthesized compounds were characterized by IR, ^1H-NMR, and EI-MS spectra and all were screened in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme inhibition activities. Molecular docking was accomplished for these compounds to examine their binding interactions with AChE and BChE human proteins. The strategy we applied for this purpose was a direct receptor-based approach. The binding modes of the inhibitors under study were determined using an automated docking program (AutoDock) and were compared with antienzymatic IC_{50} values. Both studies confirmed the potential of compounds as excellent inhibitors for AChE and BChE.

Keywords: Ethyl piperidine-4-carboxylate, benzenesulfonyl chloride, piperidine-4-carbohydrazide, enzyme inhibition, molecular docking, spectral analysis, AChE/BChE inhibitors

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