Synthesis and Antifungal Activity of 4‐Arylamino‐1,2‐Naphthoquinones‐1,2,3‐Triazoles Hybrids

Quinones have been strategically combined with various heterocyclic scaffolds to enhance their biological properties. In this study, two new series of hybrid derivatives of 4-amino-1,2-naphthoquinones bearing a triazole ring were synthesized via a three-step procedure. These compounds were evaluated for antifungal activity and for their ability to generate reactive oxygen species (ROS). The compounds were active against both yeast and filamentous fungi. Notably, their antifungal effect was not linked to ROS generation or to interaction with lanosterol 14α-demethylase, the main accepted mechanisms of action for naphthoquinones and triazoles, respectively. The structural diversity of these 1,2-naphthoquinones enables a range of molecular interactions with fungal targets, making them promising candidates for developing novel antifungal agents, particularly given the high prevalence of fungal infections in human colonization and their clinical significance.