Abstract
In this paper, we present some elements of our optimization program to decouple triclosan's specific FabI effect from its nonspecific cytotoxic component. The implementation of this strategy delivered highly specific, potent, and nonbiocidal new FabI inhibitors. We also disclose some preclinical data of one of their representatives, 83, a novel antibacterial compound active against resistant staphylococci and some clinically relevant Gram negative bacteria that is currently undergoing clinical trials.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Infective Agents, Local / chemical synthesis
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Anti-Infective Agents, Local / pharmacology*
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Benzamides / chemical synthesis
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Benzamides / pharmacology*
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Cells, Cultured
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Dogs
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Drug Evaluation, Preclinical
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Drug Resistance, Multiple, Bacterial / drug effects*
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Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / antagonists & inhibitors*
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Gram-Negative Bacteria / drug effects*
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Humans
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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Structure
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Phenyl Ethers / chemical synthesis
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Phenyl Ethers / pharmacology*
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Rats
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Structure-Activity Relationship
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Triclosan / chemical synthesis
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Triclosan / pharmacology*
Substances
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4-(4-ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzamide
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Anti-Infective Agents, Local
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Benzamides
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Phenyl Ethers
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Triclosan
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Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)