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.
Keywords:
anti-inflammatory; antioxidants; molecular docking; pyrazolone.
© 2014 John Wiley & Sons A/S.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / pharmacology
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Anti-Inflammatory Agents / therapeutic use
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Antioxidants / chemistry
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Binding Sites
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Carrageenan / toxicity
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Catalytic Domain
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Cyclooxygenase 1 / chemistry
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Cyclooxygenase 1 / metabolism
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Cyclooxygenase 2 / chemistry*
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Cyclooxygenase 2 / metabolism
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Cyclooxygenase 2 Inhibitors / chemical synthesis*
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Cyclooxygenase 2 Inhibitors / pharmacology
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Cyclooxygenase 2 Inhibitors / therapeutic use
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Edema / chemically induced
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Edema / drug therapy
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Erythrocytes / cytology
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Erythrocytes / drug effects
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Hemolysis / drug effects
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Male
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Molecular Docking Simulation
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Nitric Oxide / chemistry
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Pyrazolones / chemistry*
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Pyrazolones / pharmacology
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Pyrazolones / therapeutic use
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Rats
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Rats, Sprague-Dawley
Substances
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Anti-Inflammatory Agents
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Antioxidants
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Cyclooxygenase 2 Inhibitors
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Pyrazolones
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Nitric Oxide
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Carrageenan
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Cyclooxygenase 1
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Cyclooxygenase 2