Details

Autor(en) / Beteiligte

• 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.

Titel

In silico studies, nitric oxide, and cholinesterases inhibition activities of pyrazole and pyrazoline analogs of diarylpentanoids

Ist Teil von

• Archiv der Pharmazie (Weinheim), 2021-01, Vol.354 (1), p.e2000161-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• 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. A new series of pyrazole, phenylpyrazole, and pyrazoline analogs was synthesized via the reaction of diarylpentanoids with hydrazine monohydrate and phenylhydrazine. The phenylpyrazole derivatives (4a–e) are potent NO inhibitors, whereas the pyrazole and pyrazoline analogs (3a, 3e, and 5a) are potent and selective butyrylcholinesterase (BChE) inhibitors. The N‐acetylated moiety, together with the hydrophobic phenyl rings, is important to elicit the BChE inhibitory capability.