New thiazolo[4,5-d]pyrimidine analogues were synthesized and biologically assessed in-vitro for their antineoplastic activity. The growth inhibitory effects of these compounds were assessed through the National Cancer Institute-United States of America (NCI-USA) anticancer screening program. Compound 5 (7-Chloro-3-(2,4-dimethoxyphenyl)-5-methylthiazolo[4,5-d]pyrimidine-2(3H)-thione) was found to have a potent and broad-spectrum cytotoxic action against NCI panel with GI₅₀ (50% growth inhibition concentration) mean graph midpoint (MG-MID) = 2.88 µM. MTT assay was used to determine IC₅₀ values of the most potent agent against HCT-116 colorectal carcinoma and WI-38 human lung fibroblast cell lines; 5.33 µM ± 0.69 and 21.69 µM ± 1.04, respectively. Flow cytometric analysis revealed that compound 5 triggered apoptosis and G2/M cell cycle arrest. The ability of compound 5 to inhibit CDK1 (Cyclin-Dependent Kinase 1)/Cyclin B complex was evaluated, and its IC₅₀ value was 97 nM ± 2.33. Moreover, according to the gene expression analysis, compound 5 up-regulated p53, BAX, cytochrome c, caspases-3,-8 and-9 besides down-regulated Bcl-2. In conclusion, compound 5 exerted a potent pro-apoptotic activity through the activation of the intrinsic apoptotic pathway and arrested the cell cycle at the G2/M phase.

合成了新的噻唑并[4，5- d ]嘧啶类似物，并对它们的抗肿瘤活性进行了体外生物学评估。通过美国国家癌症研究所（NCI-USA）的抗癌筛选计划评估了这些化合物的生长抑制作用。发现化合物 5  （7-氯-3-（2,4-二甲氧基苯基）-5-甲基噻唑并[4,5- d ]嘧啶-2（3 H）-硫酮）具有有效的广谱细胞毒作用具有GI ₅₀（50％生长抑制浓度）的NCI面板平均图中点（MG-MID）= 2.88 µM。使用MTT测定法测定IC ₅₀最有效的抗HCT-116大肠癌和WI-38人肺成纤维细胞系药物的价值；分别为5.33 µM±0.69和21.69 µM±1.04。流式细胞仪分析表明化合物 5 触发凋亡和G2 / M细胞周期停滞。评价化合物 5 抑制CDK1（细胞周期蛋白依赖性激酶1）/细胞周期蛋白B复合物的能力，其IC ₅₀值为97nM±2.33。此外，根据基因表达分析，化合物 5除了下调Bcl-2外，还 上调了p53，BAX，细胞色素c，caspases-3，-8和-9。总之，化合物 5 通过激活内在的凋亡途径发挥有效的促凋亡活性，并使细胞周期停滞在G2 / M期。