An extract of the filamentous fungus Bionectria sp. (MSX 47401) showed both promising cytotoxic activity (>90% inhibition of H460 cell growth at 20 μg/mL) and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). A bioactivity-directed fractionation study yielded one new peptaibol (1) and one new tetramic acid derivative (2), and the fungus biosynthesized diverse secondary metabolites with mannose-derived units. Five known compounds were also isolated: clonostachin (3), virgineone (4), virgineone aglycone (5), AGI-7 (6), and 5,6-dihydroxybisabolol (7). Compounds 5 and 7 have not been described previously from natural sources. Compound 1 represents the second member of the peptaibol structural class that contains an ester-linked sugar alcohol (mannitol) instead of an amide-linked amino alcohol, and peptaibols and tetramic acid derivatives have not been isolated previously from the same fungus. The structures of the new compounds were elucidated primarily by high-field NMR (950 and 700 MHz), HRESIMS/MS, and chemical degradations (Marfey’s analysis). All compounds (except 6) were examined for antibacterial and antifungal activities. Compounds 2, 4, and 5 showed antimicrobial activity against S. aureus and several MRSA isolates.
NCBI PubMed ID: 23806109Publication DOI: 10.1021/np3008842Journal NLM ID: 7906882Publisher: American Society of Pharmacognosy
Correspondence: Nicholas_Oberlies@uncg.edu
Institutions: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, USA, Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, USA, Department of Pharmaceutical Sciences, BRITE, North Carolina Central University, Durham, USA, Natural Products Laboratory, Research Triangle Institute, Research Triangle Park, USA, Mycosynthetix Inc., Hillsborough, USA
Methods: 13C NMR, 1H NMR, HPLC, UV, optical rotation measurement, CD, TOCSY, cytotoxicity assay, HMBC, antimicrobial assay, NOESY, HR-ESI-MS/MS
Found