Abstract
Maesanin, a metabolite isolated from the fruit of Maesa lanceolata (Myrsinaceae), was devoid of antifungal activity. However, when maesanin was combined with sub-inhibitory concentrations of a sesquiterpene dialdehyde polygodial known to affect the fungal cell membrane, antifungal activity was observed. The synergistic growth inhibition in malt extract medium differed according to fungal species. Among the yeasts tested, Candida utilis was shown to be susceptible to the combination of maesanin and polygodial, but Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Hansenula anomala were not. Synergistic action was also observed in the inhibition of cellular respiration of C. utilis. In mitochondrial preparations from C. utilis or rat liver, maesanin alone significantly inhibited NADH oxidase, succinate oxidase, NADH-cytochrome c reductase, succinate-cytochrome c reductase, and succinate-dichlorophenol-indophenol reductase. Polygodial alone had no inhibitory effect on the respiratory chain enzymes. These results suggest that the synergistic effect of polygodial is due to an increased permeability of maesanin through the cell membrane. The antifungal activity of maesanin in combination with polygodial appears to result from respiratory inhibition with its site of action near coenzyme Q of the mitochondrial electron transport system.