Antifungal activity of chalcones from Zuccagnia punctata Cav. acting against clinically important fungi and studies of mechanism of action.

LAURA SVETAZ; MARÍA BELEN AGÜERO; SANDRA ALVAREZ; LORENA LUNA; GABRIELA FERESIN; MARCOS DERITA; ALEJANDRO TAPIA; SUSANA ZACCHINO

PLANTA MEDICA

Georg Thieme, Verlag KG . Sttutgart Nueva York

Lugar: Nueva York; Año: 2007 vol. 73 p. 1074 - 1080

0032-0943

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 - 250 ƒÊg/mL) and very strong antifungal activities against the dermatophytes M. gypseum, T. rubrum and T. mentagrophytes (MICs: 8 - 16 ƒÊg/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Œ,4Œ-dihydroxy-3Œ-methoxychalcone (1) and 2Œ,4Œ-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 ~ MFC and does not act by inhibiting the fungal cell wall. So, 2Œ,4Œ-dihydroxychalcone 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.