Screening and Antifungal Activity of a -Carboline Derivative against and .

Background: Cryptococcosis is a fungal disease of bad prognosis due to its pathogenicity and the toxicity of the drugs used for its treatment. The aim of this study was to investigate the medicinal potential of carbazole and -carboline alkaloids and derivatives against and .

Methods: MICs were established in accordance with the recommendations of the Clinical and Laboratory Standards Institute for alkaloids and derivatives against and genotypes VNI and VGI, respectively. A single active compound was further evaluated against . genotypes VNII, VNIII, and VNIV, . genotypes VGI, VGIII, and VGIV, ATCC 36232, for cytotoxicity against the MRC-5 lineage of human fibroblasts and for effects on fungal cells (cell wall, ergosterol, and leakage of nucleic acids).

Results: Screening of 11 compounds revealed 8-nitroharmane as a significant inhibitor (MIC 40 g/mL) of several and genotypes. It was not toxic to fibroblasts (IC > 50 g/mL) nor did it alter fungal cell walls or the concentration of ergosterol in or . It increased leakage of substances that absorb at 260 nm.

Conclusions: The synthetic -carboline 8-nitroharmane significantly inhibits pathogenic species and is interesting as a lead compound towards new therapy for infections.