Abstract
A series of hybrid compounds possessing an nNOS pharmacophore linked to an antioxidant fragment has been synthesized. Among them, compound 8d, a propofol derivative, displayed the greatest dual potencies against nNOS (IC(50)=0.12 microM) and lipid peroxidation (IC(50)=0.4 microM) accompanied with e/nNOS selectivity (67.5). This shows that nNOS was able to accommodate very bulky groups such as di-tert-butyl or di-iso-propyl phenol in its active site.
MeSH terms
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Antioxidants / chemical synthesis*
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Antioxidants / pharmacology*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Lipid Peroxidation / drug effects
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Lipoxygenase Inhibitors / chemical synthesis
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Lipoxygenase Inhibitors / pharmacology
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase Type I
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Nitric Oxide Synthase Type III
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Propofol / analogs & derivatives
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Propofol / chemical synthesis
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Propofol / pharmacology
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Substrate Specificity
Substances
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Antioxidants
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Enzyme Inhibitors
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Lipoxygenase Inhibitors
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nitric Oxide Synthase Type III
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Propofol