EFFICACY OF POMEGRANATE PEEL EXTRACT IN COMBINATION WITH AZOLE DRUGS AGAINST MYCOTOXIGENIC FUNGI

Natural sources have been important for the development of new active molecules for many years. Various small molecules with unique chemical structure and potent bioactivities were discovered through various sources like plants, marine products, and microorganisms. A number of potent antifungals have been originated from various natural sources. However, very little is known about anti-mycotoxigenic activity of natural compounds. Recently we prepared crude methanolic extracts from the fruit peel of Punica granatum, which exhibited antifungal activity against mycotoxigenic fungi, such as Aspergillus flavus, A. parasiticus, A. fumigatus, Fusarium verticillioides, F. proliferatum, and human pathogenic yeasts Candida albicans. Minimal inhibitory concentration (MIC) of the crude extract determined by broth microdilution method as recommended by CLSI protocol, and ranged between 2.4 – 1250 µg/ml. The combinations of the extract and azole fungicides lead to additive and synergistic interactions against these fungi with fractional inhibitory concentration (FIC) index range of 0.25 to 1. MIC for azole drugs (prochloraz and propiconazole) decreased at least twofold when combined with the extract. The synergism observed in disk-diffusion and checkerboard assays was confirmed in time-kill curves. The combination of the natural compounds with azole antifungals represents an attractive prospect for the development of new management strategies against mycotoxigenic fungi, and should be investigated further in in vivo models.