Design, Synthesis, Investigation, and Biological Activity Assessments of (4-Substituted-Phenyl)-<i>N</i>-(3-morpholinopropyl)-3-phenylthiazol-2(3<i>H</i>)-imine Derivatives as Antifungal Agents

Haji Ali S., OSMANİYE D., Saglik B. N., LEVENT S., ÖZKAY Y., KAPLANCIKLI Z. A.

ACS OMEGA, sa.38, ss.39326-39343, 2024 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1021/acsomega.3c07879
  • Dergi Adı: ACS OMEGA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Directory of Open Access Journals
  • Sayfa Sayıları: ss.39326-39343
  • Anadolu Üniversitesi Adresli: Evet

Özet

In this study, a series of novel thiazol-2(3H)-imine (2a-2j) were designed, synthesized, and characterized by means of 1H NMR, 13C NMR, and HRMS spectral analyses. In vitro antifungal activity was performed using a modified EUCAST protocol. Two of the synthesized compounds (2d and 2e) showed activity against Candida albicans and Candida parapsilosis. Compound 2e showed activity against C. parapsilosis (MIC50 = 1.23 mu g/mL) for 48 h. This value is very similar to ketoconazole. The dynamic analysis of the potential compounds 2d and 2e revealed notable stability while interacting with the 14 alpha-demethylase enzyme substrate. The absorption, distribution, metabolism, and excretion (ADME) studies of the candidate compound showed acceptable ADME parameter data and verified their drug-likeness characteristics. According to the results of this study, compound 4-(4-fluorophenyl)-N-(3-morpholinopropyl)-3-phenylthiazol-2(3H)-imine (2e) and its derivatives as 14 alpha-demethylase inhibitors can be used as a new antifungal for further structural improvements and additional research.