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

SVETAZ, L.; AGÜERO, M.; ALVAREZ, S.; LUNA, L.; FERESIN, G.; DERITA, M.; TAPIA, A.; ZACCHINO, S.

PLANTA MEDICA

Nahrstedt A

Lugar: Stuttgart, Germany; Año: 2007 vol. 73 p. 1074 - 1080

0032-0943

Abstract Petrol 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 ug/mL) and very strong antifungal activities against the dermatophytes M. gypseum, T. rubrum and T. mentagrophytes (MICs 8-16 ug/mL) thus supporting the ethnopharamcological 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 fungicide rather than fungistatic, do not disrupt the fungal membranes up to 4x MFC and do not act by inhibiting the fungal cell-wall. So, 2,4-dihydroxychalcone would act by a different mechanism of action than the antifungal drugs in current clinical use, such as amphotericin B, azoles or echinocandins, appearing very promising as a novel antifungal agent.