Abstract
New glycolipids and a benzylammonium lipid were rationally designed by varying the chemical structure of a D-glucose-derived hit compound active as lipid A antagonist. We report the synthesis of these compounds, their in vitro activity as lipid A antagonists on HEK cells, and the capacity to inhibit LPS-induced septic shock in vivo. The lack of toxicity and the good in vivo activity suggest the use of some compounds of the panel as hits for antisepsis drug development.
MeSH terms
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Anti-Infective Agents / chemical synthesis*
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Anti-Infective Agents / pharmacology
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Benzylammonium Compounds / chemical synthesis*
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Benzylammonium Compounds / pharmacology
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Cell Line
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Drug Design
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Glycolipids / chemical synthesis*
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Glycolipids / pharmacology
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Humans
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Lipid A / antagonists & inhibitors
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Lipids / chemical synthesis*
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Lipids / pharmacology
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Sepsis / drug therapy*
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Shock, Septic / drug therapy
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Structure-Activity Relationship
Substances
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Anti-Infective Agents
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Benzylammonium Compounds
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Glycolipids
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Lipid A
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Lipids