Abstract
A series of novel acrylic acid derivatives bearing at the 3 position thienyl, furfuryl and 3,5-ditert-butyl-4-hydroxyphenyl substituents have been designed, synthesized and tested as potential dual lipoxygenase/cyclooxygenase-1 (LOX/COX-1) inhibitors and as antioxidant and anti-inflammatory agents. Some compounds have shown moderate antioxidant and COX-1 inhibitory activities, very good anti-inflammatory activity and an inhibition of soybean lipoxygenase (LOX) higher than caffeic acid. In particular, compound 4I disclosed a moderate in vitro LOX inhibition with an IC(50) = 100 μM whereas compounds 1I and 2II exhibited the best, albeit poor, activity as COX-1 inhibition (75% inhibition at 100 μM). Good radical scavenging properties were shown by compounds 4I, 3I and 1II. Docking simulations performed on LOX inhibitor 4I and COX-1 inhibitor 1I indicated that hydrophobic key interactions may govern the enzyme-inhibitor binding.
Copyright © 2010 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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Acrylates / chemical synthesis*
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Acrylates / chemistry
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Acrylates / pharmacology*
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Acrylates / therapeutic use
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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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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / pharmacology*
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Antioxidants / therapeutic use
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Binding Sites
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Cyclooxygenase 1 / chemistry
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Cyclooxygenase 1 / metabolism*
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Cyclooxygenase Inhibitors / chemical synthesis
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Cyclooxygenase Inhibitors / chemistry
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Cyclooxygenase Inhibitors / pharmacology*
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Cyclooxygenase Inhibitors / therapeutic use
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Drug Design*
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Female
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Free Radical Scavengers / chemical synthesis
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Free Radical Scavengers / chemistry
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Free Radical Scavengers / pharmacology
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Free Radical Scavengers / therapeutic use
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Glycine max / enzymology
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Inflammation / drug therapy
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Lipoxygenase / chemistry
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Lipoxygenase / metabolism
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Lipoxygenase Inhibitors / chemical synthesis
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Lipoxygenase Inhibitors / chemistry
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Lipoxygenase Inhibitors / pharmacology*
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Lipoxygenase Inhibitors / therapeutic use
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Male
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Models, Molecular
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Protein Conformation
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Rats
Substances
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Acrylates
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Anti-Inflammatory Agents
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Antioxidants
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Cyclooxygenase Inhibitors
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Free Radical Scavengers
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Lipoxygenase Inhibitors
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Lipoxygenase
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Cyclooxygenase 1
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acrylic acid