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

Fungal infections are a growing global health concern due to rising incidence and increasing resistance to existing drugs. This study introduces a series of novel coumarin-chalcone hybrids linked via a 1,2,3-triazole moiety, aiming to develop new antifungal candidates. The hybrids were synthesized using Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC), with optimized conditions yielding 75–85%. In silico ADMET analysis predicted favorable pharmacokinetic properties, suggesting their potential as drug-like candidates. Molecular docking studies revealed strong binding interactions with sterol 14α-demethylase, a crucial enzyme in fungal ergosterol biosynthesis, indicating their potential as antifungal agents. All synthesized compounds showed relatively more negative binding energy compared to 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 ADMET properties, and strong binding interactions with sterol 14α-demethylase. They are viable leads for further biological evaluation and potential therapeutic applications.

Publication History

Received: 28 February 2025

Accepted after revision: 07 April 2025

Accepted Manuscript online:
07 April 2025