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

Autor: Shabaan MA; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt., Kamal AM; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, October University for Modern Science and Arts (MSA), Giza, Egypt., Faggal SI; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt., Elsahar AE; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt., Mohamed KO; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2020 Apr; Vol. 353 (4), pp. e1900308. Date of Electronic Publication: 2020 Feb 07.
DOI: 10.1002/ardp.201900308
Abstrakt: 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.
(© 2020 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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