Evaluation of the Antifungal Properties of Azomethine-Pyrazole Derivatives from a Structural Perspective.

About 95 % of candidiasis infections worldwide are attributed to five Candida fungi species, with C. albicans being the most prevalent and severe. Due to resistance phenomena, the last decade has seen a significant challenge for candidiasis treatment with antifungal drugs, which has led to an urgent need for new antifungal agents. In this article, we report the synthesis of a series of azomethine-pyrazole derivatives bearing a para-substituted azo-phenyl ring. These compounds were evaluated as antifungal agents against Candida species and Cryptococcus neoformans strains. Compound ClAzoNH, substituted by chloride, displayed the highest toxicity on Candida albicans, with an MIC50 value of 2.08 μg/mL, while methoxy-substituted MeOAzoNH showed moderate inhibitory activity. The unsubstituted AzoNH compound exhibited the highest activity towards Candida tropicalis, Candida glabrata, Candida parapsilosis, and Candida krusei strains. In the case of C. albicans, the CaCYP51 protein appears to be the most probable biological target, while for C. neoformans, interactions with the CnFTase protein explained the in vitro results.