Abstract
Two new compounds, designated paraphaeosphaeride D (1) and berkleasmin F (2) together with a previously known compound, berkleasmin A (3), isolated from a culture broth of the fungus Paraphaeosphaeria sp. TR-022, proved to be new circumventors of arbekacin (ABK) resistance in methicillin-resistant Staphylococcus aureus (MRSA). The structures of 1 and 2 were elucidated by spectroscopic analyses, including various NMR experiments. All compounds showed 10-100 times ABK circumvention activities using the paper disc method and reduced the MIC values of ABK against MRSA from 16 μg ml(-1) to 4 μg ml(-1) (fourfold) using the agar dilution method. These new compounds might be promising lead compounds for developing circumventors of ABK resistance in MRSA.
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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Ascomycota / metabolism*
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Dibekacin / analogs & derivatives
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Dibekacin / pharmacology
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Drug Resistance, Bacterial
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Lactams / chemistry
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Lactams / isolation & purification
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Lactams / pharmacology*
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Magnetic Resonance Spectroscopy
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Methicillin-Resistant Staphylococcus aureus / drug effects*
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Microbial Sensitivity Tests
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Pyrones / chemistry
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Pyrones / isolation & purification
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Pyrones / pharmacology*
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Sesquiterpenes / chemistry
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Sesquiterpenes / isolation & purification
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Sesquiterpenes / pharmacology*
Substances
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Anti-Bacterial Agents
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Lactams
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Pyrones
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Sesquiterpenes
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berkleasmin A
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berkleasmin F
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paraphaeosphaeride D
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Dibekacin
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arbekacin