Abstract
24 derivatives (5a-x) derived from natural pyranochalcones (I and II) were designed and evaluated for their inhibitory potency on the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells. Among them, four compounds (5b, 5d, 5f, and 5h) exhibited more potent inhibitory effects on iNOS activity and iNOS-mediated NO production than a positive control indomethacin. Furthermore, 5b could significantly suppress the progression of carrageenan-induced hind paw edema compared to indomethacin at a dosage of 10 mg/kg/day, and dose-dependently ameliorated the development of adjuvant-induced arthritis (AIA) validated by arthritic scores and H&E staining of joints. In addition, docking study confirmed that 5b was an iNOS inhibitor with binding to the active site of murine iNOS.
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
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 / metabolism
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Anti-Inflammatory Agents / pharmacology*
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Anti-Inflammatory Agents / therapeutic use
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Arthritis, Experimental / drug therapy
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Benzopyrans / chemical synthesis*
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Benzopyrans / metabolism
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Benzopyrans / pharmacology*
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Benzopyrans / therapeutic use
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Carrageenan / pharmacology
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Catalytic Domain
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Cell Line
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Chalcone / chemical synthesis*
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Chalcone / metabolism
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Chalcone / pharmacology*
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Chalcone / therapeutic use
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Chalcones / chemical synthesis*
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Chalcones / metabolism
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Chalcones / pharmacology*
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Chalcones / therapeutic use
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Chemistry Techniques, Synthetic
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Drug Design*
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Edema / chemically induced
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Edema / drug therapy
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Male
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Mice
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Molecular Docking Simulation
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Nitric Oxide Synthase Type II / antagonists & inhibitors
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Nitric Oxide Synthase Type II / chemistry
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Nitric Oxide Synthase Type II / metabolism
Substances
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Anti-Inflammatory Agents
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Benzopyrans
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Chalcones
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Chalcone
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Carrageenan
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Nitric Oxide Synthase Type II