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

Sazan Haji Ali; Derya Osmaniye; Begüm Nurpelin Sağlık; Serkan Levent; Yusuf Özkay; Zafer Asım Kaplancıklı

doi:10.1021/acsomega.3c07879

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. eCollection 2024 Sep 24.

Authors

Sazan Haji Ali^{1

2}, Derya Osmaniye^{3

4}, Begüm Nurpelin Sağlık^{3

4}, Serkan Levent^{3

4}, Yusuf Özkay^{3

4}, Zafer Asım Kaplancıklı³

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.

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.