Abstract
The antimicrobial lipopeptides polymyxin B and E (colistin) are being used as a 'last-line' therapy for infections caused by multidrug-resistant Gram-negative pathogens. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections caused by the Gram-negative 'superbugs'. This report details the structure-activity relationships (SAR) based design, in toto synthesis, and preclinical evaluation of a series of novel polymyxin lipopeptides with better antibacterial activity against polymyxin-resistant Gram-negative bacteria.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology*
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Anti-Bacterial Agents / therapeutic use
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Drug Resistance, Multiple, Bacterial
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Gram-Negative Bacteria / drug effects*
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Gram-Negative Bacterial Infections / drug therapy
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Humans
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Mice
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Microbial Sensitivity Tests
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Models, Molecular
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Polymyxins / chemistry*
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Polymyxins / pharmacology*
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Polymyxins / therapeutic use
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Pseudomonas Infections / drug therapy
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Pseudomonas aeruginosa / drug effects
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Polymyxins