Antifungal potential, mechanism of action, and toxicity of 1,4-naphthoquinone derivatives.

Background: The rising prevalence of fungal infections and challenges such as adverse effects and resistance against existing antifungal agents have driven the exploration of new antifungal substances. Methods: We specifically investigated naphthoquinones, known for their broad biological activities and promising antifungal capabilities. It specifically examined the effects of a particular naphthoquinone on the cellular components of Candida albicans ATCC 60193. The study also assessed cytotoxicity in MRC-5 cells, Artemia salina, and the seeds of tomatoes and arugula. Results: Among four tested naphthoquinones, 2,3-DBNQ (2,3-dibromonaphthalene-1,4-dione) was identified as highly effective, showing potent antifungal activity at concentrations between 1.56 and 6.25 μg mL-1. However, its cytotoxicity in MRC-5 cells (IC50 = 15.44 µM), complete mortality in A. salina at 50 μg mL-1, and significant seed germination inhibition suggest limitations for its clinical use. Conclusions: The findings indicate that primary antifungal mechanism of 2,3-DBNQ might involve disrupting fungal membrane permeability, which leads to increased nucleotide leakage. This insight underscores the need for further research to enhance the selectivity and safety of naphthoquinones for potential therapeutic applications.