Design, Synthesis, DFT, Molecular Docking, and Biological Evalution of Pyrazole Derivatives as Potent Acetyl Cholinestrease Inhibitors

• Published in: Journal of molecular structure 2023-01, Vol.1271, p.134137, Article 134137
• Main Authors: Abdelwahab, Huda E., Ibrahim, Hesham Z., Omar, Alaa Z.
• Format: Article
• Language: English
• Subjects: Acetylcholinstrease; Alzheimer's; Furan; Molecular Docking; Pyrazole
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.134137

•New pyrazole derivatives were successfully synthesized from formyl furan derivatives.•The density functional theory (DFT) calculations were performed.•The purified pyrazoline derivatives were in-vitro screened for their acetyl cholinesterase (AChE) inhibitory activities using Ellman's method.•Molecular docking was performed via the MOE (2015) for the active sites of Acetyl cholinesterase from Homo sapiens (PDB: 4M0E) to predict the binding mode.•The newly synthesized compound showed inhibition effect on Acetyl Cholinestrease . Alzheimer's disease (AD) is an age-related chronic and progressive neurodegenerative disease, affecting cognition, memory, and behavior. Treatment of Alzheimer's disease's (AD) symptoms has been done in several viable therapeutic ways; one of them is enhancing the neurotransmissions in the nervous system, such as acetylcholine. Acetylcholine is hydrolyzed into acetate and choline by acetylcholinesterase (AChE). In order to delay the hydrolysis of acetylcholine to take its transmission rule; AChE inhibitors were used to prevent the fast hydrolysis of acetylcholine by interacting with the enzyme rather than acetylcholine. In light of that, a new series of pyrazole molecules were synthesised and examined as potential AchE inhibitors. The target pyrazole compounds were synthesised from the reaction of formyl furan derivatives with acetophenone to give chalcone, followed by reaction with hydrazinehydrate and condensation with different aldehydes. The purified pyrazole derivatives were in-vitro screened for their acetyl cholinesterase (AChE) inhibitory activities using Ellman's method. The pyrazole derivative containing benzylidene moiety inhibited the AChE enzyme with an IC50 value of 5.28 M. Molecular docking studies were performed to test their activities against AchE. The density functional theory (DFT) calculations were performed to estimate the thermal parameters, dipole moment, polarizability, chemical reactivity descriptors, and molecular electrostatic potential of the prepared pyrazoline at the B3LYP/6-311G level of theory. [Display omitted]