Evaluation of antifungal spectrum of Cupferron against Candida albicans

Candida albicans is an opportunistic yeast accounting for about 50-90 % of all cases of candidiasis in humans, ranging from superficial to systemic potentially life-threatening infections. The presence of several virulence factors, including biofilm, hyphal transition, and proteolytic enzymes production, worsens the fungal infections burden on healthcare system resources. Hence, developing new bioactive compounds with antifungal activity is a pressing urgence for the scientific community. In this perspective, we evaluated the anti-Candida potential of the N-Nitroso-N-phenylhydroxylamine ammonium salt (cupferron) against standard and clinical C. albicans strains. Firstly, the in vitro cytotoxicity of cupferron was checked in the range 400-12.5 μg/mL against human microglial cells (HMC-3). Secondly, its antifungal spectrum was explored via disk diffusion test, broth-microdilution method, and time-killing curve analysis, validating the obtained results through scanning electron microscopy (SEM) observations. Additionally, we evaluated the cupferron impact on the main virulence determinants of Candida albicans. At non-toxic concentrations (100-12.5 μg/mL), the compound exerted interesting anti-Candida activity, registering a minimum inhibitory concentration (MIC) between 50 and 100 μg/mL against the tested strains, with a fungistatic effect until 100 μg/mL. Furthermore, cupferron was able to counteract fungal virulence at MIC and sub-MIC values (50-12.5 μg/mL). These findings may propose cupferron as a new potential antifungal option for the treatment of Candida albicans infections.