Chalcone–Coumarin Polymers: Synthesis and Antifungal Evaluation with Docking Studies

This study aimed to investigate the in vitro activity the antifungal activity of chalcone-coumarin-based heterocyclic polymers (8a–8e) against four clinically relevant fungal strains: Candida albicans, Aspergillus niger, Cryptococcus neoformans, and Fusarium solani. Using MIC₅₀ values with fluconazole as the reference drug, the study highlighted the superior antifungal potential of these polymers, particularly 8c, which demonstrated significantly lower MIC₅₀ values compared to fluconazole against C. albicans (12.31 ± 0.85 µg/mL vs. 28.51 ± 1.98 µg/mL) and F. solani (13.57 ± 0.79 µg/mL vs. 30.92 ± 2.12 µg/mL). The enhanced efficacy of compound 8c is attributed to the synergistic effects of chalcone and coumarin moieties, which improve membrane disruption, ergosterol biosynthesis inhibition, and enzymatic interference. Polymer 8e also showed potent activity, particularly against C. albicans (14.72 ± 0.96 µg/mL) and F. solani (16.89 ± 0.87 µg/mL), then the fluconazole. While 8a and 8b exhibited moderate activity, 8b showed comparable activity to fluconazole against A. niger (50.39 ± 3.12 µg/mL vs. 35.88 ± 2.04 µg/mL). Polymer 8d showed intermediate efficacy, especially against C. albicans (19.84 ± 1.23 µg/mL) and F. solani (16.34 ± 1.09 µg/mL). Polymer 8a shows a significantly higher binding affinity (–8.92 kcal/mol) toward fungal Nmt protein compared to fluconazole (–5.44 kcal/mol), suggesting stronger and more stable interactions. These findings underscore the potential of chalcone-coumarin heterocyclic polymers as promising antifungal agents, with 8c and 8e being particularly effective against resistant strains.