Abstract
Fifteen new depsidone-based analogues named spiromastixones A-O (1-15) were isolated from the fermentation broth of a deep-sea Spiromastix sp. fungus. Their structures were elucidated on the basis of extensive NMR and mass spectroscopic analysis in association with chemical conversion. Spiromastixones A-O are classified into two subtypes based on the orientation of ring C relative to ring A, while the n-propyl substituents on rings A and C are rarely seen in natural products. Most analogues are substituted by various numbers of chlorine atoms. All compounds exhibited significant inhibition against Gram-positive bacteria including Staphylococcus aureus, Bacillus thuringiensis, and Bacillus subtilis with MIC values ranging from 0.125 to 8.0 μg/mL. In addition, compounds 6-10 displayed potent inhibitory effects against methicillin-resistant bacterial strains of S. aureus (MRSA) and S. epidermidis (MRSE), while 10 also inhibited the growth of the vancomycin-resistant bacteria Enterococcus faecalis and E. faecium (VRE). The structure-activity relationships are discussed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Depsides / chemistry
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Depsides / isolation & purification*
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Depsides / pharmacology*
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Enterococcus faecalis / drug effects
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Fungi / chemistry*
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Gram-Positive Bacteria / drug effects
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Heterocyclic Compounds, 3-Ring / chemistry
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Heterocyclic Compounds, 3-Ring / isolation & purification*
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Heterocyclic Compounds, 3-Ring / pharmacology*
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Hydrocarbons, Chlorinated / chemistry
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Hydrocarbons, Chlorinated / isolation & purification*
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Hydrocarbons, Chlorinated / pharmacology*
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Lactones / chemistry
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Lactones / isolation & purification*
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Lactones / pharmacology*
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Methicillin / pharmacology
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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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Nuclear Magnetic Resonance, Biomolecular
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Oceans and Seas
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Staphylococcus aureus / drug effects
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Structure-Activity Relationship
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Vancomycin / pharmacology
Substances
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Anti-Bacterial Agents
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Depsides
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Heterocyclic Compounds, 3-Ring
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Hydrocarbons, Chlorinated
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Lactones
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depsidone
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Vancomycin
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Methicillin