Pestalone, a new antibiotic produced by a marine fungus in response to bacterial challenge.
The isolation and structure determination of a new chlorinated benzophenone antibiotic, pestalone (1), is described. The new compound was produced by a cultured marine fungus only when a unicellular marine bacterium, strain CNJ-328, was co-cultured in the fungal fermentation. The fungus, isolated from the surface of the brown alga Rosenvingea sp. collected in the Bahamas Islands, was identified as an undescribed member of the genus Pestalotia. The structure of 1, initially assigned with only modest confidence by combined spectral and chemical data, was confirmed by single-crystal X-ray analysis. Pestalone (1) exhibits moderate in vitro cytotoxicity in the National Cancer Institute's 60 human tumor cell line screen (mean GI(50) = 6.0 microM). More importantly, pestalone shows potent antibiotic activity against methicillin-resistant Staphylococcus aureus (MIC = 37 ng/mL) and vancomycin-resistant Enterococcus faecium (MIC = 78 ng/mL), indicating that pestalone should be evaluated in advanced models of infectious disease.
Cueto
M
M
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093-0204, USA.
Jensen
P R
PR
Kauffman
C
C
Fenical
W
W
Lobkovsky
E
E
Clardy
J
J
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001444:Bahamas; D001577:Benzophenones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D016984:Enterococcus faecium / Q000378:metabolism; D016106:Methicillin Resistance; D003904:Mitosporic Fungi / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D000459:Phaeophyceae; D013056:Spectrophotometry, Ultraviolet; D013211:Staphylococcus aureus / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D001577:Benzophenones; C442628:pestalone