ABT-751衍生物的合成及其抗肿瘤活性的研究

Synthesis and cytotoxicity research of ABT- 751 derivatives

目的探索ABT-751衍生物的构效关系,寻找抗肿瘤活性高的化合物。方法以2-氯-3-硝基吡啶为原料与芳基伯胺反应,胺化产物经过硝基还原和芳基磺酰反应,得到新ABT-751的衍生物;用磺酰罗丹明(SRB)法测定新衍生物对人肺癌细胞A549的增殖抑制活性。结果与结论合成了18个ABT-751衍生物,初步体外的抗肿瘤活性显示:化合物Ⅴk、Ⅴo和Ⅴq的IC50分别为0.99、0.67、0.05μmol·L-1,具良好的体外抗肿瘤活性。

OBJECTIVE To study on the structure - activity relationship of the ABT - 751 derivatives. METHODS Synthesis was started with the ammoniation of 2 - ehloro - 3 - nitropyridine and aromatic amines. The aminating products went through reduction and aryl - sulfonation to give the target molecules. The in vitro cytotoxicity of these new derivatives were tested in human lung cancer cell line A549. RESULTS and CONCLUSION Eighteen new derivatives were prepared, IC50 of these derivatives are 0.99μmol·L^-1, 0. 67 μmol·L^-1 and 0.05 μmol·L^-1, respectively, indicating that these compounds had potent cytotoxicity.