西松烷型二萜衍生物的合成及抗肿瘤活性研究

Synthesis and evaluation of cembranoid type diterpene derivatives as potential antitumor agents

目的基于西松烷型二萜天然产物新巴豆瑞士松酸进行结构修饰,并对得到的衍生物进行体外抗肿瘤活性评价。方法以新巴豆瑞士松酸为起始原料,通过缩合反应、点击化学反应得到目标化合物。采用噻唑蓝(MTT)法考察所合成的目标化合物对HeLa、K562和K562A/02肿瘤细胞的抗增殖活性。结果合成了11个文献未报道的新巴豆瑞士松酸衍生物,其结构经~1H-NMR、^(13)C-NMR及HR-MS确定。活性测试结果表明,部分衍生物表现出一定的抗肿瘤活性,其中,化合物2f对HeLa细胞表现出良好活性,化合物2e对K562和耐药的K562A/02细胞表现出良好活性。结论部分衍生物对耐药的K562A/02细胞表现出抗肿瘤活性,具有进一步研究价值。

Objective To modify the structure of neocrotocembraneic acid, a cembranoid type diterpene, and evaluate the antitumor activities of the derivatives. Methods Taking neocrotocembraneic acid as starting material, the target compounds were synthesized by condensation reaction and click reaction. Their antitumor activities in vitro on HeLa, K562, and K562A/02 were evaluated by MTT. Results Eleven novel derivatives were synthesized which have not been reported in any literature and the structures were characterized by ^1H-NMR,^13C-NMR, and ESI-MS. MTT assay showed that some cembrane derivatives exhibited antitumor activities. In particular, compound 2f showed good antitumor activity against HeLa and compound 2e showed promising antitumor activity against K562 and K562A/02. Conclusion Some derivatives have demonstrated promising antitumor activities against K562/A02 cell lines which are worth further studying.