Gao Dongmei, Shi Lele, Huang Yuhang, Lv Yingmei, Yang Xuan, Du Zhenting
Yangling Vocational & Technical College, Yangling 712100, China.
School of Chemistry and Pharmacy, Northwest A & F University, Yangling 712100, China.
Molecules. 2025 Apr 7;30(7):1643. doi: 10.3390/molecules30071643.
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- biological activities of these synthetic compounds on five kinds of at different concentrations were detected by the microdilution method. In the first round, four derivatives of 2-amino-4, 5-diarylthiazole exhibited moderate anti- activity. Among them, was chosen to be subjected to a demethylation process. Thus, was synthesized successfully, giving anti- activity (MIC = 9 μM) similar to that of a typical antifungal drug, fluconazole. To understand the mechanism of anti-, molecular docking of the most active against four target proteins of anti- 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.
噻唑杂环是各类药物中最常见的部分之一。以2-氨基噻唑为核心结构，氨基通过酰胺进行官能化。结果，合成了30种三取代的2-氨基-4,5-二芳基噻唑衍生物，在C2、C4和C5位置引入了不同的取代基。通过微量稀释法检测了这些合成化合物在不同浓度下对五种[具体生物名称缺失]的抗生物活性。在第一轮实验中，四种2-氨基-4,5-二芳基噻唑衍生物表现出中等抗[具体生物名称缺失]活性。其中，[具体化合物名称缺失]被选择进行去甲基化过程。因此，[具体化合物名称缺失]成功合成，其抗[具体生物名称缺失]活性（MIC = 9 μM）与典型抗真菌药物氟康唑相似。为了了解抗[具体生物名称缺失]的机制，对最具活性的[具体化合物名称缺失]针对抗[具体生物名称缺失]的四种靶蛋白，如谷氨酰胺-果糖-6-磷酸酰胺转移酶（GFAT）、蛋白激酶（Yck2）、热休克蛋白90（Hsp90）和羊毛甾醇14α-去甲基酶（CYP51）进行了分子对接。我们的研究将为新型氨基噻唑主导的药物分子的进一步设计提供实验依据和理论指导。
