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

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.

Cyclization of arylhydrazones of cross-conjugated enynones: synthesis of luminescent styryl-1H-pyrazoles and propenyl-1H-pyrazoles

“…3 Among them there are certain distinctive substances containing the 2-arylvinyl (styryl) group at various positions of a heterocycle, as well as their analogs. 4 Styrylpyrazoles, styrylpyrazolines and similarly structured substances possess antitumor, 5 antioxidative, 5 l,o ,6 antibacterial, 7 antimalarial, 8 antifungal, 9 and anti-inflammatory 10 properties, and some other types of biological activities 11 (also see the references in the review by Gomes and coworkers 4 for details). Furthermore, styrylpyrazoles have valuable photophysical abilities.…”

Hemicurcuminoids (1-styryl-1,3-diketones) – valuable multi-faceted building blocks for organic synthesis

“…The obtained pyrazoles 75a–i were successfully tested in vivo in albino mice and rats for analgesic and anti-inflammatory activities which were found to be higher than those of reference drugs – pentazocine and indomethacin, respectively (Scheme 50). A similar series of pyrazoles 75j–s was obtained by the group of Faudzi et al 100 in order to assess their anti-inflammatory activity and cholinesterase inhibition (Scheme 50).…”

“…Among the substances obtained by the group of Faudzi et al (Scheme 50), 100 ( E )-4-methoxy-2-(1-phenyl-5-styryl-1 H -pyrazol-3-yl)phenol 75q and ( E )-2-(5-(4-chlorostyryl)-1-phenyl-1 H -pyrazol-3-yl)-4-methoxyphenol 75s possessed the highest NO inhibitory effect, while ( E )-2-(5-styryl-1 H -pyrazol-3-yl)phenol 75j was the most selective inhibitor of BChE over AChE (Fig. 11).…”

Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations

“…The hunt for new analogs with desirable pharmacological profiles is a never-ending task in drug discovery programs. With the available literature on pyrazole analogs ( Fadaly et al, 2020 ; Mohamed et al, 2020 ; Azimi et al, 2021 ; Faudzi et al, 2021 ; Verma et al, 2021 ), it is relatively easy for medicinal chemists to proceed with rational synthesis or modification capable of enhancing biological activities. The substitutions, additions, or removal of functional groups are effective strategies for designing biologically important analogs.…”