Exploring medium and long arm extensions of 1,2,4-triazole derivatives as Candida albicans 14α-demethylase (CYP51) inhibitors

Alsulaimany, Marwa, Binjubair, Faizah A., Tatar, Esra, Kelly, Diane E, Kelly, Steven, Warrilow, Andrew G, Keniya, Mikhail V., Monk, Brian C., Parker, Josie E. and Simons, Claire ORCID: https://orcid.org/0000-0002-9487-1100 2025. Exploring medium and long arm extensions of 1,2,4-triazole derivatives as Candida albicans 14α-demethylase (CYP51) inhibitors. RSC Medicinal Chemistry 10.1039/D4MD00863D

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Abstract

Fungal infections have been described as a silent crisis affecting more than one billion people each year. At least 150 million of these cases involve severe and life threatening invasive fungal infections, accounting for approximately 1.7 million deaths annually. 1,2,4-Trizoles such as fluconazole and posaconazole are widely used antifungal agents, but azole resistance is an increasing problem requiring further study. 1,2,4-Triazole derivatives with medium and long arm extensions designed to bind within the Candida albicans CYP51 (CaCYP51) access channel were synthesised to study their inhibition of CaCYP51 (IC50, MIC) and binding affinity (Kd). A long arm extension using the amide linker was found to be most effective (e.g. 13), giving an antifungal profile vs. wild-type and resistant model fungal strains comparable with posaconazole.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Pharmacy Schools > Biosciences
Publisher:	Royal Society of Chemistry
ISSN:	2632-8682
Date of First Compliant Deposit:	20 March 2025
Date of Acceptance:	11 March 2025
Last Modified:	25 Mar 2025 12:30
URI:	https://orca.cardiff.ac.uk/id/eprint/177024

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