title: Synthesis and biologic evaluation of substituted 5-methyl-2-phenyl-1H-pyrazol-3(2H)-one derivatives as selective COX-2 inhibitors: molecular docking study.
abstract: The present study reported the synthesis and biologic evaluation of new pyrazolone derivatives for COX-2 inhibitory activities and investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw edema model as well as in vitro using HRBC membrane stabilization and protein denaturation method. Eight derivatives showed pronounced COX-2 inhibition, and 5a, 5d, and 5f exhibited the highest COX-2 inhibition. The derivatives were further evaluated for antioxidant activity wherein 5a and 5b showed potent free radical-scavenging activity against DPPH, nitric oxide, and hydrogen peroxide radicals. Molecular docking study revealed the binding orientations of pyrazolone derivatives into the active sites of COX-2 and thereby helps to design the potent inhibitors.
authors.affiliation: Department of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad-431001, Maharashtra, India.
authors.forename: Pritam N
authors.initials: PN
authors.lastname: Dube
authors.forename: Shweta S
authors.initials: SS
authors.lastname: Bule
authors.forename: Santosh N
authors.initials: SN
authors.lastname: Mokale
authors.forename: Manoj R
authors.initials: MR
authors.lastname: Kumbhare
authors.forename: Pravin R
authors.initials: PR
authors.lastname: Dighe
authors.forename: Yogesh V
authors.initials: YV
authors.lastname: Ushir
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry; D001665:Binding Sites; D002351:Carrageenan / Q000633:toxicity; D020134:Catalytic Domain; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D008297:Male; D062105:Molecular Docking Simulation; D009569:Nitric Oxide / Q000737:chemistry; D047069:Pyrazolones / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D047069:Pyrazolones; D009569:Nitric Oxide; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: anti-inflammatory; antioxidants; molecular docking; pyrazolone