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

In this study, a series of novel thiazol-2(3)-imine (-) were designed, synthesized, and characterized by means of H NMR, C NMR, and HRMS spectral analyses. In vitro antifungal activity was performed using a modified EUCAST protocol. Two of the synthesized compounds ( and ) showed activity against and . Compound showed activity against (MIC = 1.23 μg/mL) for 48 h. This value is very similar to ketoconazole. The dynamic analysis of the potential compounds and 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)--(3-morpholinopropyl)-3-phenylthiazol-2(3)-imine () and its derivatives as 14α-demethylase inhibitors can be used as a new antifungal for further structural improvements and additional research.