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In silico studies, nitric oxide, and cholinesterases inhibition activities of pyrazole and pyrazoline analogs of diarylpentanoids
Author(s) -
Mohd Faudzi Siti Munirah,
Leong S. Wei,
Auwal Faruk A.,
Abas Faridah,
Wai Lam K.,
Ahmad Syahida,
Tham Chau L.,
Shaari Khozirah,
Lajis Nordin H.,
Yamin Bohari M.
Publication year - 2021
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.202000161
Subject(s) - pyrazole , chemistry , pyrazoline , acetylcholinesterase , butyrylcholinesterase , phenylhydrazine , nitric oxide , docking (animal) , quinoline , aché , stereochemistry , combinatorial chemistry , enzyme , biochemistry , organic chemistry , medicine , nursing
Abstract A new series of pyrazole, phenylpyrazole, and pyrazoline analogs of diarylpentanoids (excluding compounds 3a , 4a , 5a , and 5b ) was pan‐assay interference compounds‐filtered and synthesized via the reaction of diarylpentanoids with hydrazine monohydrate and phenylhydrazine. Each analog was evaluated for its anti‐inflammatory ability via the suppression of nitric oxide (NO) on IFN‐γ/LPS‐activated RAW264.7 macrophage cells. The compounds were also investigated for their inhibitory capability toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), using a modification of Ellman's spectrophotometric method. The most potent NO inhibitor was found to be phenylpyrazole analog 4c , followed by 4e , when compared with curcumin. In contrast, pyrazole 3a and pyrazoline 5a were found to be the most selective and effective BChE inhibitors over AChE. The data collected from the single‐crystal X‐ray diffraction analysis of compound 5a were then applied in a docking simulation to determine the potential binding interactions that were responsible for the anti‐BChE activity. The results obtained signify the potential of these pyrazole and pyrazoline scaffolds to be developed as therapeutic agents against inflammatory conditions and Alzheimer's disease.