Funicone-related compounds, potentiators of antifungal miconazole activity, produced by Talaromyces flavus FKI-0076

Abstract

Talaromyces flavus FKI-0076, a soil isolate, was found to produce compounds which reinforce the anti-Candida albicans activity of miconazole. Four structurally related compounds, a novel one, designated actofunicone, and the knowns deoxyfunicone, vermistatin and NG-012, were isolated from the culture broth by solvent extraction, ODS column chromatography and HPLC. The structure of actofunicone was elucidated as benzoic acid, 3,5-dimethoxy-2-[[4-oxo-6-(2-acetyloxy propyl)-4H-pyran-3-yl]carbonyl]-,methyl ester by various spectroscopic analyses including NMR experiments. These compounds potentiated the anti-C. albicans activity of miconazole, decreasing the IC50 value of miconazole from 19 μM to 1.6-3.7 μM in the presence of the funicones.