三尖杉碱和桥氧三尖杉碱衍生物的合成及抗肿瘤活性

Synthesis and antitumor activity of the derivatives of cephalotaxine and drupacine

摘要: 目的为了充分利用我国的三尖杉属植物资源,寻找高效低毒的抗肿瘤药物。方法对三尖杉碱和桥氧三尖杉碱进行了C₃位的结构修饰,合成了C₃具有紫杉醇侧链及其对映体的新酯碱化合物。结果共得到6个新化合物。药理筛选表明,化合物VIIIa,VIIIb,IXa和IXc对KB,HCT和Bel具有较高的细胞毒作用。结论新酯碱值得进一步探讨研究。

Abstract: AimTo make full use of cephalotaxus plant resources and search for antitumor agents with higher activities and lower side effects. MethodsThe C₃ hydroxy groups of the cephlotaxine and drupacine were acylated by taxol side chain and its isomers to give a series of derivatives of cephlotaxine and drupacine. ResultsSix novel alkaloid esters were designed and synthesized. The pharmacological screening results showed that VIIIa, VIIIb, IXa and IXc exhibited significant activities on KB, HCT and Bel in vitro. Conclusion Novel alkaloid esters are worthy to be intensively studied.