摘要
本文以索拉非尼为先导化合物进行结构改造,合成了一系列苄基脲类化合物。采用MTT法对目标化合物进行了体外抗肿瘤活性筛选,药理结果显示部分化合物对多种人肿瘤细胞的抑制作用与索拉非尼相当,其中化合物20和23分别针对HT-29和MX-1肿瘤细胞的抑制作用的IC50值达微摩尔水平,明显优于阳性对照药索拉非尼,尤其是酰胺部分含3-吡啶基的化合物20,不仅具有较强的抑制HT-29活性,其IC50值为3.82μmol·L-1,而且溶解度与索拉非尼相比有较明显的提高,值得进一步研究。
A novel series of benzyl urea analogues based on the structural modification of sorafenib were synthesized. Their in vitro antitumor activities against MX-1, HepG2, Ketr3 and HT-29 were evaluated using the standard MTT assay. While several target compounds showed inhibitory activity against multiple cancer cell lines, compound 9 was of particular interest, demonstrating IC50 values （5.69-13.6 μmol＇L-1） comparable to those of sorafenib. Furthermore, compounds 20 and 23 showed more potent inhibitory activity against HT-29 and MX-1 when compared to sorafenib. In particular, compound 20 bearing the N-3-pyridyl moiety not only exhibited greater inhibitory activity against HT-29 cell line （IC 50 3.82 μmol L-1）, but also had improved solubility at pH 7.2, is worthy of further investigation as a lead to identify novel antitumor agents.
出处
《药学学报》
CAS
CSCD
北大核心
2013年第5期709-717,共9页
Acta Pharmaceutica Sinica
基金
Project supported by the National Science&Technology Major Project(2009ZX09301-003-9-1)
关键词
苄基脲化合物
索拉非尼
结构改造
抗肿瘤活性
benzyl urea derivative
sorafenib
structural modification
antitumor activity
