Compound 5p(Yunnan University of Chinese Medicine)

Candida albicans infections are becoming increasingly prevalent, making the development of new drugs an urgent priority. In this study, a series of new aminopiperidine-azole derivatives were designed, synthesized, and evaluated for their in vitro antifungal activity against both FLC-sensitive and -resistant strains of C. albicans. Several compounds exhibited good antifungal activity, with compound 5p demonstrating the most promising efficacy against the sensitive strain SC5314 (MIC₅₀ = 0.28 μM). Mechanism studies revealed that 5p significantly inhibited biofilm formation and hyphal growth by downregulating key genes of the cAMP-PKA signaling pathway, including RAS1, EFG1, BCR1, ECE1, and HWP1. Furthermore, 5p showed low cytotoxicity against human bronchial epithelial cells (16HBE) at effective concentrations. These findings suggest that 5p is a promising lead compound for the development of new antifungal drugs.