Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, People's Republic of China.
Anticancer Drugs. 2012 Oct;23(9):914-22. doi: 10.1097/CAD.0b013e328354dc85.
Our initial study showed the potent cytotoxic effects of a series of new chiral 2-(ethylthio)-thiazolone analogues we synthesized. In the present study, we used computer prediction and found that nitro functionality and the modification of substituents R could further improve their activities in the presence of the nitro group. Compound 1s with nitro, naphthyl, ethyl groups, and a chiral center was predicted to be the most effective. We showed that compound 1s could inhibit the growth of five different cancer cell lines in a time-dependent and dose-dependent manner. 1s could induce Hela cell apoptosis by activating the mitochondria apoptotic pathway. In addition, 1s could inhibit the proliferation, migration, tuber formation, and adhesion of human umbilical vein endothelial cells, suggesting its antiangiogenesis effects. Furthermore, we confirmed the in-vivo antitumor effects of 1s on sarcoma S-180-bearing mice. Taken together, chiral 2-(ethylthio)-thiazolone analogue 1s is a promising compound for further anticancer drug development.
我们的初步研究表明，我们合成的一系列新型手性 2-（乙硫基）-噻唑啉类似物具有很强的细胞毒性。在本研究中，我们通过计算机预测发现，硝基功能和取代基 R 的修饰可以进一步提高它们在存在硝基时的活性。预测具有硝基、萘基、乙基和手性中心的化合物 1s 是最有效的。我们表明，化合物 1s 可以通过激活线粒体凋亡途径，以时间和剂量依赖的方式抑制五种不同癌细胞系的生长。1s 可以诱导 Hela 细胞凋亡。此外，1s 可以抑制人脐静脉内皮细胞的增殖、迁移、结节形成和黏附，提示其具有抗血管生成作用。此外，我们证实了 1s 对肉瘤 S-180 荷瘤小鼠的体内抗肿瘤作用。综上所述，手性 2-（乙硫基）-噻唑啉类似物 1s 是一种很有前途的抗癌药物开发化合物。
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