The thiazole heterocycle is one of the most common moieties found in various drugs. Using 2-aminothiazole as the core structure, the amino group was functionalized with an amide. As a result, 30 trisubstituted 2-amino-4, 5-diarylthiazole derivatives were synthesized, with different substitutions introduced at the C2, C4, and C5 positions. The anti-Candida albicans biological activities of these synthetic compounds on five kinds of Candida albicans at different concentrations were detected by the microdilution method. In the first round, four derivatives of 2-amino-4, 5-diarylthiazole exhibited moderate anti-Candida albicans activity. Among them, 4a8 was chosen to be subjected to a demethylation process. Thus, 5a8 was synthesized successfully, giving anti-Candida albicans activity (MIC80 = 9 μM) similar to that of a typical antifungal drug, fluconazole. To understand the mechanism of anti-Candida albicans, molecular docking of the most active 5a8 against four target proteins of anti-Candida albicans, such as glutamine-fructose-6-phosphoamidamitransferase (GFAT), protein kinase (Yck2), heat-shock protein 90 (Hsp90), and lanosterol 14a-demethylase (CYP51) was carried out. Our research will provide an experimental basis and theoretical guidance for the further design of a new aminothiazole-leading pharmaceutical molecule.
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