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

Alsulaimany M., Binjubair F. A., TATAR E., Kelly D. E., Kelly S. L., Warrilow A. G., ...More

RSC Medicinal Chemistry, vol.16, no.5, pp.2270-2280, 2025 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 16 Issue: 5
  • Publication Date: 2025
  • Doi Number: 10.1039/d4md00863d
  • Journal Name: RSC Medicinal Chemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core
  • Page Numbers: pp.2270-2280
  • Marmara University Affiliated: Yes

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.