Antifungal constituents of Curtisia dentata and Maytenus undata active against Cryptococcus neoformans and Candida albicans

There is a critical need for new antifungal drugs following increasing drug resistance, undesirable side-effects, toxicity and costs of current drugs. Active natural products from plants, or standardized plant extracts, may potentially provide new therapeutic preparations. Opportunistic fungal pathogens such as Candida and Cryptococcus species often infect immunocompromised patients and also cause disease in domesticated animals.

In a broad screening programme, antifungal activity in Curtisia dentata and Maytenus undata leaf extracts was detected. A broth microdilution assay was used to define minimum inhibitory concentration (MIC) values against Cryptococcus neoformans and Candida albicans. Cytotoxic activity against Vero cells in a colorimetric cell viability (MTT) assay was also investigated. Using bioassay-directed fractionation, lupeol and betulinic acid were isolated from C. dentata. Betulinic acid presented higher antifungal activity than lupeol against C. neoformans and C. albicans, with MIC values of 32 and 16µg/ml compared to 180 and 250µg/ml for lupeol, respectively. The activity of betulinic acid was not as good as that of the standard drug amphotericin B (MIC=0.16µg/ml against both fungi). However, the compounds were also relatively cytotoxic, with selectivity index (SI) values less than 1. From Maytenus undata, several antifungal triterpenes were isolated, but these showed simultaneous cytotoxicity (SI values below 1).

Evaluation of the selectivity of potential antifungals by parallel cytotoxicity testing is a useful tool in the discovery of plant-derived antifungals, although toxicity may possibly be reduced by structural modification if bioactivity is promising following mechanism of action studies.

Acknowledgements: Claude Leon Foundation, National Research Foundation (South Africa).