1,5-Diarylidene-4-piperidones as Promising Antifungal Candidates Against<em> Cryptococcus neoformans</em>

The study investigates the antifungal potential of 1,5-diarylidene-4-piperidones. These compounds were synthesized via Claisen-Schmidt condensation, yielding 26 derivatives with varied electronic and hydrophobic properties. Their antifungal efficacy against Cryptococcus neoformans was evaluated using minimum inhibitory concentration (MIC) assay, revealing that piperidone with tetrabutoxy groups exhibited potent activity (MIC of 7.8 µM), surpassing standard antifungals like fluconazole. The selectivity index (SI) values confirmed their safety profile across various human cell lines. Mechanistic insights via docking studies suggest that these compounds inhibit ergosterol biosynthesis by targeting sterol 14-demethylase, with E binding score of 8.2 close to that of fluconazole. The compounds also demonstrated broad-spectrum activity against other pathogenic yeasts and fungi, including Candida and Aspergillus species, with some efficacy against fluconazole-resistant strains. These findings underscore the potential of 1,5-diarylidene-4-piperidones as promising antifungal candidates with a favorable safety profile.