Abstract
Four aaptamines (1-4), 1H-benzo[de][1,6]-naphthyridine alkaloids, were isolated from the marine sponge Aaptos aaptos and their inhibitory activities against sortase A (SrtA), an enzyme that plays a key role in cell wall protein anchoring and virulence in Staphylococcus aureus, were evaluated. Isoaaptamine (2) was a potent inhibitor of SrtA, with an IC(50) value of 3.7+/-0.2 microg/mL. The suppression of fibronectin-binding activity by isoaaptamine (2) highlights its potential for the treatment of S. aureus infections via inhibition of SrtA activity. Our studies have identified a series of SrtA inhibitors, providing the basis for further development of potent inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminoacyltransferases / antagonists & inhibitors*
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Animals
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Anti-Bacterial Agents / isolation & purification
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Anti-Bacterial Agents / pharmacology
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Bacterial Proteins / antagonists & inhibitors*
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Chromatography, Gel
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Chromatography, High Pressure Liquid
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Cysteine Endopeptidases
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology*
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Fibronectins / metabolism
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Microbial Sensitivity Tests
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Naphthyridines / isolation & purification
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Naphthyridines / pharmacology*
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Porifera / chemistry*
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Protein Binding
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Staphylococcus aureus / drug effects
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Staphylococcus aureus / growth & development
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Enzyme Inhibitors
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Fibronectins
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Naphthyridines
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Aminoacyltransferases
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sortase A
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Cysteine Endopeptidases
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aaptamine