Abstract
A series of maleimide analogs bearing benzenesulfonamide were synthesized (4a-r). The anti-inflammatory activity of synthesized derivatives was evaluated using carrageenan induced rat paw edema model. COX-1 and COX-2 potency was evaluated through in vitro cyclooxygenase assays. The results revealed that, compounds 4a, 4h, 4 j, 4 k and 4r had potent COX-2 percentage inhibition as well as in vivo anti-inflammatory activity. The potent compound 4 j was docked into the COX-2 active site to determine the probable binding model. The results of in vivo and in vitro studies demonstrate that phenyl ring with electron withdrawing groups on maleimide ring would generate more potent anti-inflammatory agents. Thus, these compounds can serve as potential leads for further anti-inflammatory studies.
Keywords:
COX-2; Carrageenan paw edema; Docking; Maleimide; Ulcerogenic effects.
Copyright © 2015 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemical synthesis
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Anti-Inflammatory Agents / chemistry*
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Anti-Inflammatory Agents / pharmacology*
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Anti-Inflammatory Agents / therapeutic use
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Benzenesulfonamides
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Carrageenan
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Cyclooxygenase 1 / metabolism
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Cyclooxygenase 2 / metabolism
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Cyclooxygenase 2 Inhibitors / chemical synthesis
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Cyclooxygenase 2 Inhibitors / chemistry*
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Cyclooxygenase 2 Inhibitors / pharmacology*
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Cyclooxygenase 2 Inhibitors / therapeutic use
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Drug Design
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Edema / chemically induced
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Edema / drug therapy
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Humans
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Maleimides / chemical synthesis
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Maleimides / chemistry*
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Maleimides / pharmacology*
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Maleimides / therapeutic use
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Molecular Docking Simulation
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Rats
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
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Sulfonamides / therapeutic use
Substances
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Anti-Inflammatory Agents
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Cyclooxygenase 2 Inhibitors
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Maleimides
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Sulfonamides
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maleimide
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Carrageenan
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Cyclooxygenase 1
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Cyclooxygenase 2