Design, synthesis and investigation of new imidazole derivatives with biological activities and antifungal effects

Peçe S., OSMANİYE D., SAĞLIK ÖZKAN B. N., LEVENT S., ÖZKAY Y., KAPLANCIKLI Z. A.

Journal of Biomolecular Structure and Dynamics, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1080/07391102.2025.2490059
  • Dergi Adı: Journal of Biomolecular Structure and Dynamics
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core
  • Anahtar Kelimeler: 14α-demethylase, Antifungal, imidazole, molecular docking, molecular dynamics
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Evet

Özet

Fungal infections are important types of infection that annually cause the death of many people around the world. Therefore, new antifungal agents that are more effective and less toxic are constantly needed. In this study, new imidazole derivatives were synthesized and their antifungal activities were investigated. Compound 5d showed antifungal activity against Candida albicans, Candida parapsilosis and Candida krusei with a minimum inhibitory concentration (MIC50) of 0.98 µg/mL. While compound 5e showed antifungal effects against C. albicans and C. parapsilosis with MIC50 of 0.98 µg/mL, it displayed potent antifungal activity against C. krusei with MIC50 of 1.96 µg/mL. Compound 5h exhibited antifungal activity against C. albicans and C. parapsilosis with MIC50 of 1.96 and 0.98 µg/mL, respectively. It is known that azole group antifungals inhibit ergosterol biosynthesis by inhibiting the 14α-demethylase enzyme. For this reason, in the present study in silico studies were performed on 14α-demethylase enzyme crystal (PDB ID: 1EA1). Molecular docking and dynamics studies were conducted to examine the binding modes of the active compounds (5d, 5e and 5h). The results of the in silico studies agreed with the biological activity results.