Antifungal activity of Zuccagnia punctata Cav.:: Evidence for the mechanism of action

Petroleum ether and dichloromethane extracts of fruits, aerial parts and exudate of Zuccagnia punctata Cav. (Fabaceae) showed moderate antifungal activities against the yeasts C albicans, S. cerevisiae and C neoformans (MICs: 62.5-250pg/mL) and very strong antifungal activities against the dermatophytes M. gypseum, T rubrum and T. mentagrophytes (MICs: 8-16 mu g/mL) thus supporting the ethnopharmacological use of this plant. Antifungal activity-directed fractionation of active extracts by using bioautography led to the isolation of 2,4-dihydroxy-3 -methoxychalcone (1) and 2,4 -dihydroxychalcone (2) as the compounds responsible for the antifungal activity. Second-order studies included MIC80, MIC50 and MFC of both chalcones in an extended panel of clinical isolates of the most sensitive fungi, and also comprised a series of targeted assays. They showed that the most active chalcone 2 is fungicidal rather than fungistatic, does not disrupt the fungal membranes up to 4 x MFC and does not act by inhibiting the fungal cell wall. So, 2,4Ldihydroxychalcone would act by a different mechanism of action than the antifungal drugs in current clinical use, such as amphotericin B, azoles or echinocandins, and thus appears to be very promising as a novel antifungal agent.