Synthesis of 2-Amino-4, 5-Diarylthiazole Derivatives and Evaluation of Their Anti-Candida Albicans Activity

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-<i>Candida albicans</i> biological activities of these synthetic compounds on five kinds of <i>Candida albicans</i> at different concentrations were detected by the microdilution method. In the first round, four derivatives of 2-amino-4, 5-diarylthiazole exhibited moderate anti-<i>Candida albicans</i> activity. Among them, <b>4a8</b> was chosen to be subjected to a demethylation process. Thus, <b>5a8</b> was synthesized successfully, giving anti-<i>Candida albicans</i> activity (MIC₈₀ = 9 μM) similar to that of a typical antifungal drug, fluconazole. To understand the mechanism of anti-<i>Candida albicans</i>, molecular docking of the most active <b>5a8</b> against four target proteins of anti-<i>Candida albicans,</i> 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.