Abstract
Platensimycin (1a) and platencin (2) are inhibitors of FabF and FabF/H bacterial fatty acid synthase. The discovery of natural congeners is an approach that can render a better understanding of the structure-function relationships of complex natural products. The isolation and structure elucidation of nine new congeners (11-20) of platensimycin and platencin are described from a fermentation broth of Streptomyces platensis. These hydroxylated congeners are likely derived by cytochrome P450 oxidation of the terpenoid units post-cyclization. Polar groups in the terpenoid portion of the molecule produce negative interactions with the hydrophobic pocket of FabF, resulting in poor activities. However, the discovery of these compounds serves an important purpose, not only to understand structure-function relationships, which cannot be easily accessed by chemical modification, but also to provide access to compounds that could be used for structural identification/confirmation of the oxidative trace metabolites produced in vivo during animal experiments.
MeSH terms
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Adamantane / chemistry*
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Adamantane / isolation & purification
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Adamantane / pharmacology
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Aminobenzoates / chemistry*
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Aminobenzoates / isolation & purification
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Aminobenzoates / pharmacology
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Aminophenols / chemistry*
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Aminophenols / isolation & purification
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Aminophenols / pharmacology
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Anilides / chemistry*
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Anilides / isolation & purification
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Anilides / pharmacology
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / isolation & purification
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Anti-Bacterial Agents / pharmacology
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Cytochrome P-450 Enzyme System / metabolism
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Fatty Acid Synthase, Type II / antagonists & inhibitors
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Methicillin-Resistant Staphylococcus aureus / drug effects
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Microbial Sensitivity Tests
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Molecular Structure
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Polycyclic Compounds / chemistry*
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Polycyclic Compounds / isolation & purification
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Polycyclic Compounds / pharmacology
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Stereoisomerism
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Streptomyces / chemistry*
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Structure-Activity Relationship
Substances
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Aminobenzoates
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Aminophenols
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Anilides
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Anti-Bacterial Agents
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Polycyclic Compounds
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Cytochrome P-450 Enzyme System
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Fatty Acid Synthase, Type II
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Adamantane
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platensimycin
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platencin