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New Generation Modified Azole Antifungals against Multidrug-Resistant <i>Candida auris</i>

Yiyuan Chen, Yunxiao Li, Kazi S. Nahar, Md. Mahbub Hasan, Caleb Marsh Orcid Logo, Melanie Clifford, Godwin A. Aleku Orcid Logo, Steven Kelly, David Lamb Orcid Logo, Chengetai Diana Mpamhanga Orcid Logo, Ilias Kounatidis, Ajit J. Shah, Charlotte K. Hind Orcid Logo, J. Mark Sutton, Khondaker Miraz Rahman Orcid Logo

Journal of Medicinal Chemistry, Volume: 68, Issue: 13, Pages: 14054 - 14071

Swansea University Authors: Steven Kelly, David Lamb Orcid Logo

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DOI (Published version): 10.1021/acs.jmedchem.5c01253

Abstract

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 heteroalipha...

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Published in: Journal of Medicinal Chemistry
ISSN: 0022-2623 1520-4804
Published: American Chemical Society (ACS) 2025
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa69875
Abstract: 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.
College: Faculty of Medicine, Health and Life Sciences
Funders: Funding was received from the China Scholarship Council (CSC) and a Medical Research Council Confidence in Concept grant (award code MC_PC_13065).
Issue: 13
Start Page: 14054
End Page: 14071

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