ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Zijingang Campus, Hangzhou 310058, China.
Eur J Med Chem. 2011 Mar;46(3):919-26. doi: 10.1016/j.ejmech.2011.01.007. Epub 2011 Jan 15.
We reported the synthesis, hypoxic cytotoxic activities and selectivities of 18 new 3-(alkoxymethylamino)-1,2,4-benzotriazine 1,4-dioxides. The synthesized compounds were screened in vitro against 5 cell lines: K562, SMMC-7721, A549, PC-3 and KB in hypoxia and in normoxia. Some of them showed higher or similar cytotoxic activity when compared to tirapazamine. Physico-chemical study showed the positive correlation between hypoxic activity and lipophilicity within a certain range. Preliminary mechanism study on the potent derivatives 4b, 4l and 4m indicated that the cytotoxic activities of these compounds might be mediated by inducing apoptosis.
我们报道了 18 种新的 3-(烷氧基甲基氨基)-1,2,4-苯并三嗪 1,4-二氧化物的合成、低氧细胞毒性活性和选择性。合成的化合物在体外进行了筛选，针对 5 种细胞系：K562、SMMC-7721、A549、PC-3 和 KB 在低氧和常氧条件下进行筛选。与替拉扎明相比，其中一些化合物表现出更高或相似的细胞毒性活性。物理化学研究表明，在一定范围内，低氧活性与亲脂性之间存在正相关关系。对有效衍生物 4b、4l 和 4m 的初步机制研究表明，这些化合物的细胞毒性活性可能是通过诱导细胞凋亡介导的。
