Fusapyrone

Novel fusapyrone analogs, deoxyneofusapyrone and 7-desmethyldeoxyneofusapyrone were isolated from a pathogenic fungus, Verticillium dahliae, which causes Verticillium wilt disease in Helianthus annuus. Spectral analyses revealed that these are 2-pyrone type analogs of deoxyfusapyrone and its 7-desmethyl derivative, respectively. Biological assay disclosed that 10microg of deoxyneofusapyrone inhibited the growth of MRSA clinical isolate 87-7927.

Fusapyrone (1) and deoxyfusapyrone (2) are two 3-substituted-4-hydroxy-6-alkyl-2-pyrones isolated from Fusarium semitectum that have considerable antifungal activity against molds. Because of their low zootoxicity and selective action they are potentially utilizable along with biocontrol yeasts for control of postharvest crop diseases. Seven derivatives of 1 (3 and 5-10) and one derivative of 2 (4) were obtained by chemical modifications of the glycosyl residue, the 2-pyrone ring, the aliphatic chain, or a combination thereof, and a structure-activity correlation study was carried out with regard to their zootoxicity and antifungal activity. Derivatives 7-10, as well as 1, were slightly zootoxic in Artemia salina (brine shrimp) bioassays, whereas pentaacetylation of 1 into 3, 5, and 6 resulted in a strong increase in toxicity. Compound 4, the tetraacetyl derivative of 2, was as toxic as 2. Because the structural changes of 1 that resulted in an increase of biological activity in A. salina bioassay were those that affected mainly the water solubility of the molecule, it appears that toxicity is related to hydrophobicity. Compounds 1 and 2 showed strong antifungal activity toward Botrytis cinerea, Aspergillus parasiticus, and Penicilliun brevi-compactum (minimum inhibitory concentration at 24 h = 0.78-6.25 microg/mL). Among derivatives 3-10, only compounds 7, 9, and 10 retained some activity, limited to B. cinerea and at high concentration (25-50 microg/mL). None of the compounds 1-10 inhibited the growth of the biocontrol yeasts Pichia guilliermondii and Rhodotorula glutinis at the highest concentration tested (50 microg/mL).

Two new compounds, paecilospirone (1) and phomopsidin (2), and seven known compounds, chaetoglobosin A (3), griseofulvin (4), fusarielin A (5), fusapyrone (6), deoxyfusapyrone (7), and verrucarins J (8) and L acetate (9), have been isolated and characterized from marine-derived fungi collected in tropical and sub-tropical coral reef environments. The utility of marine-derived fungi as a source of bioactive secondary metabolites is discussed.