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

  • ACS Omega. 2024 Sep 16;9(38):39326-39343. doi: 10.1021/acsomega.3c07879.
Sazan Haji Ali  1  2 ,  Derya Osmaniye  3  4 ,  Begüm Nurpelin Sağlık  3  4 ,  Serkan Levent  3  4 ,  Yusuf Özkay  3  4 ,  Zafer Asım Kaplancıklı  3
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hawler Medical University, Erbil 44000, Iraq.
  • 2. Graduate Education Institute, Anadolu University, Eskişehir 26470, Turkey.
  • 3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
  • 4. Central Research Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
PMID: 39346840 DOI: 10.1021/acsomega.3c07879
Abstract

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 μg/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 14α-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 14α-demethylase inhibitors can be used as a new Antifungal for further structural improvements and additional research.

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