摘要
目的设计并合成达沙替尼衍生物,并研究其抗肿瘤活性。方法以达沙替尼、四乙二醇和五乙二醇单甲醚为原料,通过取代反应合成达沙替尼衍生物,并考察目标化合物对K562细胞增殖的抑制作用。结果设计并合成了4个达沙替尼衍生物,结构经~1H-NMR和MALDI-TOF-MS确证。其中2个化合物JK220324和JK220326的抗肿瘤活性较达沙替尼高,IC_(50)分别为0.50、0.34 nmol/L,较达沙替尼(0.76 nmol/L)低。结论达沙替尼用小分子聚乙二醇衍生,有望获得活性更好、毒性更小的化合物。
Objective To design and synthesize dasatinib derivatives, and study their anti-tumor activities. Methods Dasatinib, tetraethylene glycol, pentaethylene glycol monomethyl ether, and were used as materials to synthesize dasatinib derivatives by substitution reaction, and the anti-tumor activities against K562 cells were tested. Results Four dasatinib derivatives were designed and synthesized, and their structures were confirmed by 1H-NMR and MALDI-TOF-MS. In which the anti-tumor activities of two target compounds JK220324 and JK220326 were higher than dasatinib, and their IC50 were 0.50 and 0.34 nmol/L, which were lower than that of dasatinib （0.76 nmol/L）. Conclusion Dasatinib derived by low molecular polyethylene glycol derivatives is expected to acquire the compound with better activities and less toxicity.
出处
《现代药物与临床》
CAS
2017年第8期1393-1396,共4页
Drugs & Clinic
基金
天津市科技计划项目(15PTSYJC00220)
关键词
达沙替尼
慢性粒细胞白血病
合成
抗肿瘤活性
dasatinib
chronic granulocytic leukemia
synthesis
anti-tumor activity
