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-Triazoles 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.