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

Marwa Alsulaimany¹, Faizah A Binjubair¹, Esra Tatar²

¹School of Pharmacy and Pharmaceutical Sciences, Cardiff University King Edward VII Avenue Cardiff CF10 3NB UK simonsc@cardiff.ac.uk.

RSC Medicinal Chemistry

|March 26, 2025

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 (K _d). 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.

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