Design, synthesis, analgesic, anti-inflammatory activity of novel pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of COX-2/5-LOX enzymes: Histopathological and docking studies

Abdelgawad, Mohamed A.; Labib, Madlen B.; Ali, Waleed A.M.; Kamel, Gehan M.; Azouz, Amany A.; El‐Nahass, El‐Shaymaa

doi:10.1016/j.bioorg.2018.03.011

Cited by 74 publications

(27 citation statements)

References 35 publications

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“…A cluster of novel pyrazolone analogues containing aminosulfonyl group were synthesized and investigated for the anti-inflammatory potency [99]. The outcome showed that three compounds 137e139 (Fig.…”

Section: Anti-inflammatory Agentsmentioning

confidence: 99%

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Zhao

Dai

et al. 2020

European Journal of Medicinal Chemistry

149

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a b s t r a c tThe pyrazolone structural motif is a critical element of drugs aimed at different biological end-points. Medicinal chemistry researches have synthesized drug-like pyrazolone candidates with several medicinal features including antimicrobial, antitumor, CNS (central nervous system) effect, anti-inflammatory activities and so on. Meanwhile, SAR (Structure-Activity Relationship) investigations have drawn attentions among medicinal chemists, along with a plenty of analogues have been derived for multiple targets. In this review, we comprehensively summarize the biological activity and SAR for pyrazolone analogues, wishing to give an overall retrospect and prospect on the pyrazolone derivatives.

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Section: Anti-inflammatory Agentsmentioning

confidence: 99%

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Zhao

Dai

et al. 2020

European Journal of Medicinal Chemistry

149

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“…Pyrazolones are still economically important precursors for both pharmaceuticals and dyes . Pyrazolone derivatives have numerous pharmacological applications like analgesic, antipyretic, anti‐inflammatory, antibacterial, antifungal, anti‐infective, antioxidant, anticonvulsant, anti‐depressant, anti‐hyperglycemic and anti‐proliferative agents. Besides, they have the ability to extend noteworthy anticancer influences by inhibiting diverse types of enzymes that act serious roles in cell division .…”

Section: Introductionmentioning

confidence: 99%

Nano‐synthesis, characterization, modeling and molecular docking analysis of Mn (II), Co (II), Cr (III) and Cu (II) complexes with azo pyrazolone ligand as new favorable antimicrobial and antitumor agents

Gaber

Khedr

Mansour

et al. 2018

Applied Organom Chemis

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Novel nanosized Mn (II), Co (II), Cr (III) and Cu (II) complexes were synthesized with 2-((5-oxo-1,3-diphenyl-4,5-dihydro-1H-pyrazol-4-yl)diazenyl) benzoic acid, HL applying precipitation method. Their structures were characterized based on the elemental and thermal analyses, spectra (FT-IR, UV-Vis, MS, ESR and XRD), conductivity and magnetic moment measurements. IR spectra offered that HL behaves as monobasic tri-dentate ligand towards Mn (II), Cr (III) and Cu (II) and monobasic bi-dentate towards Co (II). The XRD results unambiguously confirmed the crystalline nature and nano-sized particles of Cu (II) complex while HL and other complexes exhibited amorphous phases.The magnetic moment data, UV-Vis and ESR spectra supported the formation of octahedral geometries for Mn (II), and Cr (III) complexes, whereas Co (II), and Cu (II) complexes showed tetrahedral arrangement. The activation parameters for the thermal degradation stages were theoretically calculated using TGA curves. The obtained data showed the inspected complexes as favorable antimicrobial drug candidates. The studied compounds were screened out for their antitumor and antimicrobial activities. The inspected compounds exhibited a reasonable antibacterial activity and weak antitumor efficacy. The in vitro results were confirmed using the in silico molecular docking analysis (docking server) applying x-ray crystallographic structures of the proteins (4 m01, 3 t88, 1zap & 4ynt) from PDB (Protein Data Bank). HL and probably its complexes displayed adequate binding with the receptors of 4 m01, 3 t88, 1zap, and 4ynt microorganisms. The obtained data show the inspected complexes as favorable antimicrobial drug candidates.

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“…This observation was consistent with previously published work, reporting that substitution for trimethoxy groups increased the AI activity. [ 16 ] In contrast, the grafting phenyl group in position 1 of the pyrazolone ring and the presence of sulfonamide (SO 2 NH 2 ) moiety, the most important pharmacophore for COX‐2 selectivity, [ 26,27 ] significantly improved the activity, especially in compounds 3l and 3p , which may explain its maximum selectivity against COX‐2. These results revealed that the bulkier derivatives showed better selectivity than the less bulky one based on that COX‐2 enzyme, which showed a larger pocket than COX‐1.…”

Section: Resultsmentioning

confidence: 99%

“…[ 30 ] Therefore, to elucidate the possible interactions of the most active compounds 3f , 3h , 3l , and 3p with either COX‐2 (PDB entry 1CX2) or 5‐LOX (PDB entry 3V99) receptors, a molecular docking study was carried out using Molecular Operating Environment (MOE; version 2008.10) modeling software. [ 26,31 ] Docking scores and binding interactions inside COX‐2 and 5‐LOX active sites are summarized in Table 5.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and biological evaluation of pyrazolone analogues as potential anti‐inflammatory agents targeting cyclooxygenases and 5‐lipoxygenase

Shabaan

Kamal

Faggal

et al. 2020

Archiv der Pharmazie

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New pyrazolone derivatives structurally related to celecoxib and FPL 62064 were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases (COXs) and 5‐lipoxygenase (5‐LOX) and their selectivity indices were calculated. The results showed that compounds 3f, 3h, 3l, and 3p have an excellent COX‐2 selectivity index. Moreover, they showed potent 5‐LOX inhibitory activity relative to celecoxib and zileuton, as positive controls. These promising candidates were further investigated for anti‐inflammatory activity using the carrageenan‐induced rat paw edema method and ulcerogenic liability. The results showed no ulceration, which implies their gastric safety profile. Moreover, these compounds were evaluated for prostaglandin (PGE2) production in rat serum. Molecular docking in the COX‐2 and 5‐LOX active sites was performed to rationalize their anti‐inflammatory activities. Strong binding interactions and effective docking scores were identified. The results indicated that these derivatives are good leads for dual‐acting COX‐2/5‐LOX inhibitors to be used as potent and safe anti‐inflammatory agents.

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Design, synthesis, analgesic, anti-inflammatory activity of novel pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of COX-2/5-LOX enzymes: Histopathological and docking studies

Cited by 74 publications

References 35 publications

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Nano‐synthesis, characterization, modeling and molecular docking analysis of Mn (II), Co (II), Cr (III) and Cu (II) complexes with azo pyrazolone ligand as new favorable antimicrobial and antitumor agents

Synthesis and biological evaluation of pyrazolone analogues as potential anti‐inflammatory agents targeting cyclooxygenases and 5‐lipoxygenase

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