Four novel bis-(naphtho-γ-pyrones) isolated from Fusarium species as inhibitors of HIV-1 integrase
Four novel naphtho-γ-pyrones and derivatives with coupled and strand transfer activity of HIV-1 integrase with IC50 values ranging 1–12 μM have been described.
Section snippets
Producing Organism, Fermentation and Isolation
The culture (MF6252, ATCC74396) that produced these compounds was isolated from leaf litter collected under Podocarpus dacryoides in Te Anau, New Zealand. It was identified as a Fusarium sp. and was grown in CYS80 media.7 A 1.2-L fermentation broth was extracted with methyl ethyl ketone and the extract was chromatographed on Sephadex LH-20 in MeOH yielding three consecutive fractions containing the active components. The first and third fractions were chromatographed by RPHPLC (Zorbax RX C-8,
Structure elucidation
HREIMS analysis of 1 and 2 indicated that they were isomeric and gave a parent ion at m/z 546 suggesting a molecular formula C30H26O10. The 13C NMR spectra revealed the presence of 30 carbons and supported the formula. The formula search of these compounds in the Chapman and Hall database provided chaetochromins A (5),9 B (6)9 and ustilaginoidin D (7)10 as hits which was further narrowed to the unsymmetrical dimer chaetochromin B by a 13C NMR similarity search in the SIMSER database.11
Acknowledgements
The authors thank Delia Valentino for fermentation studies.
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