Design, Synthesis, and Molecular Modeling of New and Safe Azole Oxime Esters with Promising Antifungal Activity

Yurtoğlu S., SARI S., KART D., SABUNCUOĞLU S., Saraç S.

ChemistrySelect, cilt.8, sa.18, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 8 Sayı: 18
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/slct.202300134
  • Dergi Adı: ChemistrySelect
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Anahtar Kelimeler: arylalkylazole, oxime ester, antifungal, cytotoxicity, molecular docking
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Fungal infections have become a major public health issue with dramatically increasing morbidity, mortality and cost of hospitalization. Azole antifungals are first-in-line medications against most types of mycoses and azoles having an oxime moiety, although not extensively investigated, were reported to have great antifungal potential, as well as, activity against Gram-positive bacteria. In the current study, a new series of 2-(1H-imidazol-1-yl)-1-phenylethanone oxime esters (5 a–l) were synthesized and tested for their antimicrobial activities. The sorbic acid ester (5 c) was found to be highly promising against Candida albicans and Candida parapsilosis (MIC=4 μg/ml). In addition, 5 c was not toxic to the healthy murine fibroblast. Molecular modelling suggested that the compounds were druglike, orally available, not substrates of efflux pumps, and probably acted through fungal CYP51 inhibition, which is the major action mechanism of azole antifungals.