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

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

ACS Omega, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2024
  • Doi Number: 10.1021/acsomega.3c07879
  • Journal Name: ACS Omega
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Directory of Open Access Journals
  • Bilecik Şeyh Edebali University Affiliated: Yes

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.