Abstract
Gemini compounds of the type N(alpha),N(omega)-bis(N(alpha)-lauroyl arginine)alpha,omega-alkylenediamides or bis(Args) bind bacterial lipopolysaccharide and neutralize endotoxic activity in in vitro tumor necrosis factor-alpha and nitric oxide release assays. Sequestration of lipopolysaccharide results in protection in a murine model of endotoxemia. However, the bis(Args) compounds are cytotoxic by virtue of being highly membrane-active. The development of less surface-active analogues may yield potentially therapeutically useful compounds for the treatment of Gram-negative sepsis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis*
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Amides / pharmacology*
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Animals
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Arginine / analogs & derivatives*
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Arginine / chemical synthesis
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Arginine / pharmacology
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Endotoxemia / blood
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Endotoxemia / drug therapy
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Endotoxins / antagonists & inhibitors
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Endotoxins / toxicity
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Hemolysis / drug effects
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Indicators and Reagents
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / chemistry*
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Lipopolysaccharides / toxicity
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Magnetic Resonance Spectroscopy
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Mass Spectrometry
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Mice
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Nitric Oxide / metabolism
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Amides
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Endotoxins
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Indicators and Reagents
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Lipopolysaccharides
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Tumor Necrosis Factor-alpha
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Nitric Oxide
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endotoxin, Escherichia coli
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Arginine