Chen, Y., Li, Y., Nahar, K.S., Hasan, M.M., Marsh, C., Clifford, M., Aleku, G.A., Kelly, S.L., Lamb, D.C., Mpamhanga, C.D., Kounatidis, I., Shah, A.J., Hind, C.K., Sutton, J.M., Rahman, K.M. (2025). New Generation Modified Azole Antifungals against Multidrug-Resistant Candida auris.  J. Med. Chem. 68(13): 14054--14071.

FBrf0262898

Research paper

The rise of antifungal resistance and limited treatment options highlight the urgent need for new drug classes. Candida auris is a serious global health threat with few effective therapies. In this study, novel azole-based compounds were developed by modifying the azole core with cyclic heteroaliphatic linkers connecting aromatic and heteroaromatic rings. Several compounds showed potent activity against C. auris, including azole-resistant strains, with MICs ranging from 0.016 to 4 μg/mL. The compounds also demonstrated strong activity against C. albicans, Nakaseomyces glabratus, C. tropicalis, and C. parapsilosis, with MICs mostly below 1 μg/mL. Compounds 7, 18, and 21 were more potent than fluconazole. Compound 7 inhibited CYP51, eradicated C. auris biofilms, and showed better intracellular accumulation than fluconazole. In vivo studies in Galleria mellonella and Drosophila melanogaster confirmed efficacy at 5 mg/kg and no toxicity up to 50 mg/kg, supporting further development of this scaffold against multidrug-resistant C. auris infections.

PMC12257509 (PMC) (EuropePMC)