Synthesis of some novel coumarin-based heterocycles, elucidation of their antifungal behavior, molecular docking and computational studies

Abstract

determination highlighted compounds 2 (0.35 mg/mL) and 3 (< 0.63 mg/mL) as the most potent. At the same time, molecular docking against five key fungal enzymes indicated strong, multi-target binding affinities for compounds 6-8, particularly 8, which showed ΔG values below -8.982 kcal/mol. Density Functional Theory (DFT) calculations established correlations between frontier orbital energies, energy gaps, softness, dipole moments, and antifungal performance, suggesting that reduced ΔE and enhanced softness favor the biological activity. These findings identify compound 8 as a promising broad-spectrum antifungal lead and provide valuable structure-activity insights for the rational design of coumarin-based antifungal agents.