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 - 250 microg/mL) and very strong antifungal activities against the dermatophytes M. gypseum, T. rubrum and T. mentagrophytes (MICs: 8 - 16 microg/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 MIC (80), MIC (50) 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',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, and thus appears to be very promising as a novel antifungal agent.
Svetaz
Laura
L
Farmacognosia, Facultad Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional Rosario, Rosario, Argentina.
Agüero
María Belén
MB
Alvarez
Sandra
S
Luna
Lorena
L
Feresin
Gabriela
G
Derita
Marcos
M
Tapia
Alejandro
A
Zacchino
Susana
S
D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007887:Fabaceae; D005638:Fruit; D006801:Humans; D008826:Microbial Sensitivity Tests; D003904:Mitosporic Fungi / Q000187:drug effects*; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots
D000935:Antifungal Agents; D010936:Plant Extracts