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目的探讨7H-噻唑并[3,2-b]-1,2,4-三嗪类化合物的体外肿瘤细胞增殖抑制活性,及初步的构效关系和作用机理。方法以3,4-二氢-6-芳基-3-硫代-1,2,4-三嗪-5(2H)-酮为原料,经环合反应、Williamson反应,合成7H-噻唑并[3,2-b]-1,2,4-三嗪类化合物,考察目标化合物体外肿瘤细胞增殖抑制作用。结果与结论合成了10个7H-噻唑并[3,2-b]-1,2,4-三嗪类化合物,经MS、1H-NMR确证结构。体外抗肿瘤活性研究显示,有4个化合物在50μmol·L~(-1)时对骨肉瘤细胞U2OS-EGFP抑制率高于50%。其中,活性最好的化合物4 d对U2OS-EGFP细胞抑制活性的IC50值为9.824μmol·L~(-1)。分子模拟结果显示,这类化合物作用于ERK1/2,应是一种ERK1/2抑制剂。
Objective To investigate the inhibitory activity of 7H-thiazolo [3,2-b] -1,2,4-triazines in vitro on tumor cell proliferation, as well as preliminary structure-activity relationship and mechanism. Methods 3,4-dihydro-6-aryl-3-thioxo-1,2,4-triazin-5 (2H) -one was used as starting material to synthesize 7H- [3,2-b] -1,2,4-triazines, and investigated the inhibitory effect of the target compounds on tumor cell proliferation in vitro. Results and Conclusion Ten 7H-thiazolo [3,2-b] -1,2,4-triazines were synthesized and confirmed by MS and 1H-NMR. In vitro antitumor activity study showed that 4 compounds at 50μmol·L -1 osteosarcoma cells U2OS-EGFP inhibition rate higher than 50%. Among them, IC50 value of compound 4d on U2OS-EGFP cell inhibitory activity was 9.824μmol·L -1. Molecular simulation results show that these compounds acting on ERK1 / 2 should be an ERK1 / 2 inhibitor.