Triazine-Based Small Molecules: A Potential New Class of Compounds in the Antifungal Toolbox.
Fiche publication
Date publication
janvier 2023
Journal
Pathogens (Basel, Switzerland)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DESAUBRY Laurent
Tous les auteurs :
Conrad KA, Kim H, Qasim M, Djehal A, Hernday AD, Désaubry L, Rauceo JM
Lien Pubmed
Résumé
Invasive fungal infections caused by species remain a significant public health problem worldwide. The increasing prevalence of drug-resistant infections and a limited arsenal of antifungal drugs underscore the need for novel interventions. Here, we screened several classes of pharmacologically active compounds against mammalian diseases for antifungal activity. We found that the synthetic triazine-based compound melanogenin (Mel) 56 is fungicidal in laboratory and clinical strains with minimal inhibitory concentrations of 8-16 µg/mL. Furthermore, Mel56 has general antifungal activity in several non- species and the non-pathogenic yeast . Surprisingly, Mel56 inhibited the yeast-to-hyphae transition at sublethal concentrations, revealing a new role for triazine-based compounds in fungi. In human cancer cell lines, Mel56 targets the inner mitochondrial integral membrane prohibitin proteins, PHB1 and PHB2. However, Mel56 treatment did not impact mitochondrial activity, and antifungal activity was similar in prohibitin single, double, and triple homozygous mutant strains compared to the wild-type parental strain. These results suggests that Mel56 has a novel mechanism-of-action in . Therefore, Mel56 is a promising antifungal candidate warranting further analyses.
Mots clés
Candida, antifungal, prohibitin, triazine, yeast-to-hyphae transition
Référence
Pathogens. 2023 01 12;12(1):