Microwave-Assisted Organic Synthesis, structure-activity relationship, kinetics and molecular docking studies of non-cytotoxic benzamide derivatives a...

ID: ALA4346761

Journal: Bioorg Med Chem

Title: Microwave-Assisted Organic Synthesis, structure-activity relationship, kinetics and molecular docking studies of non-cytotoxic benzamide derivatives as selective butyrylcholinesterase inhibitors.

Authors: Wajid S, Khatoon A, Khan MA, Zafar H, Kanwal S, Atta-Ur-Rahman, Choudhary MI, Basha FZ.

Abstract: A series of benzamide derivatives 1-12 with various functional groups (-H, -Br, -F, -OCH₃, -OC₂H₅, and -NO₂) was synthesized using an economic, and facile Microwave-Assisted Organic Synthesis, and evaluated for acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) activity in vitro. Structure-activity relationship showed that the substitution of -Br group influenced the inhibitory activity against BCHE enzyme. Synthesized compounds were found to be selective inhibitors of BCHE. In addition, all compounds 1-12 were found to be non-cytotoxic, as compared to the standard cycloheximide (IC₅₀ = 0.8 ± 0.2 µM). Among them, compound 3 revealed the most potent BCHE inhibitory activity (IC₅₀ = 0.8 ± 0.6 µM) when compared with the standard galantamine hydrobromide (IC₅₀ = 40.83 ± 0.37 µM). Enzyme kinetic studies indicated that compounds 1, 3-4, and 7-8 showed a mixed mode of inhibition against BCHE, while compounds 2, 5-6 and 9 exhibited an uncompetitive pattern of inhibition. Molecular docking studies further highlighted the interaction of these inhibitors with catalytically important amino acid residues, such as Glu197, Hip438, Phe329, and many others.

CiteXplore: 31378596

DOI: 10.1016/j.bmc.2019.07.015

Patent ID: ┄