荜茇明碱类似物合成与抗宫颈癌HeLa细胞活性研究

The Synthesis and Anti-cervical Cancer HeLa Cell Proliferation Activity of Piperlongumine and Its Analogues

本文设计合成了8个荜茇明碱类似物,评价了它们体外抗宫颈癌HeLa细胞增殖活性.发现将荜茇明碱中的Michael加成受体单元部分还原(PL-1和PL-2),抗宫颈癌HeLa细胞增殖活性降低7~8倍;将Michael加成受体单元完全还原(PL-3),基本无活性;而肉桂酸上取代基的改变对活性影响较小.但是,采用碳碳键将荜茇明碱中的Michael加成受体单元与内酰胺连接的类似物PL-8,48 h抗宫颈癌HeLa细胞增殖的IC_(50)值为0.61μM,比荜茇明碱活性高近12倍.这些结果为阐明荜茇明碱抗宫颈癌作用的构效关系提供了一定的基础.

Eight piperlongumine(PL)analogues were designed and synthesized,and their anti-cervical cancer HeLa cell proliferation activity in vitro were evaluated.It was found that the Michael acceptor units of PL was reduced,and its anti-cervical cancer HeLa cells proliferation activity was reduced by 7~8 times(PL-1 and PL-2).There was no Michael acceptor unit almost no activity(PL-3).The change of cinnamic acid substituent had little effect on the anti-cervical cancer HeLa cells activity.The IC_(50)of PL-8,an analogue linked to the Michael addition receptor unit and lactam in PL,was 0.61μM for 48 h against HeLa cells,nearly 12 times higher than that of PL.These results provide a basis for elucidating the structure-activity relationship of PL against cervical cancer.