Purpose: To investigate the candidacidal activity of a novel compound CF66I and attempt to elucidate
its mode of action.
Methods: Minimal inhibition concentrations (MIC) and minimal fungicidal concentrations (MFC) of CF66I for Candida albicans were determined using serial broth dilution method. Colony count assay, K+ release, propidium iodide (PI) uptake and electron microscopy were used to determine the manner in which CF66I exerts its candidacidal effects.
Results: MIC and MFC of CF66I were determined to be 5.0 - 7.0 μg/ml and 14.0 - 18.0 μg/ml. It showed strong candidacidal activity over a wide pH range (4.0-7.4). The compound killed C. albicans within 30 s. It preferentially bound to the surface of C. albicans via a specific interaction with β-1,6-glucan, one of fungal cell wall components, and then affected the normal structure of fungal cell wall and induced cell wall thickening, which was confirmed by transmission electron microscopy (TEM) CF66I also exerted its candidacidal activity against cell membrane, eventually induced K+ release from C. albicans and PI uptake. Membrane-attacking ability was also found via electron microscopy.
Conclusion: These results suggest that CF66I exerted its candidacidal activity on multiple target sites on C. albicans, and may have considerable potential for development of a new class of antifungal agents.