斑蝥素衍生物的合成、抗肝癌活性及构效关系研究

Syntheses,Activities and Structure-Activity Relationship Anti-Hepatoma of Cantharidin Derivatives

斑蝥素衍生物具有结构多样性和良好的抗肝癌活性。本文以呋喃、顺丁烯二酸酐为原料,合成了35个斑蝥素衍生物。以顺铂为阳性对照药,经MTT法测试了所合成化合物对人肝癌HepG2细胞的体外抗肿瘤活性。结果表明,化合物6d、6f、6g、6h、6i的抗肝癌活性与顺铂相当,其中,斑蝥素酰亚胺类化合物具有较好的抗肝癌活性,且当取代基为吸电子基或含氮杂环时化合物显现出较强的抗肝癌活性,该类化合物具有潜在的抗肝癌应用价值。

Based on the diversity of the structures of cantharidin derivatives and their excellent anti-hepatoma activity,thirty-five cantharidin derivatives have been synthesized starting from furan and maleic anhydride. The antihepatoma activities in vitro of the synthesized compounds were evaluated against HepG2 cell by the MTT assay. The biological results demonstrated that compounds 6 d,6 f,6 g,6 h and 6 i were commensurate with cisplatin in antihepatoma activity. The cantharidin imides showed good anti-hepatoma activity on the whole. When the substituent are electron withdrawing groups or nitrogen containing heterocycles,the compounds showed higher anti-hepatoma activity,so they may have potential application in anti-hepatoma drug discovery.