含吡啶-2-酰肼结构的索拉非尼类似物的设计、合成及其抗肿瘤活性

Design, synthesis and antitumor activity of sorafenib analogues containing 2-picolinylhydrazide moiety

摘要:
本文通过对已上市靶向抗肿瘤药 sorafenib进行结构改造, 设计合成了一系列含吡啶-2-酰肼结构的sorafenib类似物, 并采用MTT法, 评价了其对5种肿瘤细胞株的生长抑制作用。结果表明, 大多数化合物具有一定的抑制肿瘤细胞增殖的活性, 其中化合物2c、2d和2f抑制胰腺癌Mia-PaCa-2、SW1990细胞生长的作用强于阳性对照sorafenib, 化合物3f和3g对于肝癌细胞株HepG2的抑制活性是sorafenib的2～3倍, 明显优于阳性对照。

Abstract:
A novel series of sorafenib analogs containing 2-picolinyl hydrazide moiety were designed and synthesized. In vitro, most of synthesized compounds have antiproliferation activity on MDA-MB-231, ACHN, HepG2, Mia-PaCa-2 and SW1990 cell lines tested by MTT assay. It is worth noting that the antitumor activities of compounds 2c, 2d and 2f are more potent than that of sorafenib on pancreatic cancer cells Mia-PaCa-2 and SW1990, and the activities of compounds 3f and 3g are 2−3 times than that of sorafenib on human hepatocellular carcinoma HepG2 cell line.