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

In this study, a series of novel thiazol-2(3<i>H</i>)-imine (<b>2a</b>-<b>2j</b>) 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 (<b>2d</b> and <b>2e</b>) showed activity against <i>Candida albicans</i> and <i>Candida parapsilosis</i>. Compound <b>2e</b> showed activity against <i>C. parapsilosis</i> (MIC₅₀ = 1.23 μg/mL) for 48 h. This value is very similar to ketoconazole. The dynamic analysis of the potential compounds <b>2d</b> and <b>2e</b> 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)-<i>N</i>-(3-morpholinopropyl)-3-phenylthiazol-2(3<i>H</i>)-imine (<b>2e</b>) and its derivatives as 14α-demethylase inhibitors can be used as a new antifungal for further structural improvements and additional research.