Design, Synthesis, and In Silico Studies of 1,2,3-Triazole-Linked Coumarin–Chalcone Hybrids as Potential Antifungal Agents

Abstract Fungal infections are a growing global health concern due to their rising incidence and increasing resistance to existing drugs. With the aim of developing new antifungal candidates, this study introduces a series of novel coumarin–chalcone hybrids linked through a 1,2,3-triazole moiety. The hybrids were synthesized using Cu(I)-catalyzed azide–alkyne cycloaddition, with optimized conditions giving yields of 75–85%. In silico absorption, distribution, metabolism, and excretion (ADME) analysis predicted favorable pharmacokinetic properties, suggesting that the products have potential as drug-like candidates. Molecular-docking studies revealed strong binding interactions with sterol 14α-demethylase, a crucial enzyme in fungal ergosterol biosynthesis, indicating that the products have potential as antifungal agents. All the synthesized compounds showed a relatively more-negative binding energy than the standard fungicide hexaconazole, indicating their affinity for the active pocket. These triazole-linked coumarin–chalcone hybrids show promise as antifungal candidates due to their effective synthesis, favorable ADME properties, and strong binding interactions with sterol 14α-demethylase. They are, therefore, viable leads for further biological evaluation and potential therapeutic applications.