Novel Pyrone-Based Biofilm Inhibitors against Azole-Resistant Candida albicans

Candida albicans is an opportunistic fungus that is pathogenic in immunocompromised patients with life-threatening diseases such as HIV and cancer. C. albicans is the most common fungal species isolated from biofilms formed on implanted medical devices or on human tissue. Biofilm development of C. albicans is mainly driven by a transition from yeast to hyphal form involving core proteins such as HWP and ALS. We designed and synthesized novel α-pyrone-based analogues to investigate their potential in inhibiting biofilm formation and hyphal development of C. albicans. Among the synthesized compounds, three compounds (6f, 6j, and 6n) significantly inhibited C. albicans biofilm formation and reduced cell aggregation and hyphal formation in a dose-dependent manner. These compounds had minimal effects on planktonic cell growth while significantly reducing biofilm formation at 20–50 μg/mL, suggesting novel candidate compounds for managing drug-resistant strains of C. albicans. The three compounds may represent promising therapeutic options with potential synergistic effects when combined with existing antifungal agents.