喜树碱衍生物的设计合成及活性评价  

Design,Synthesis and Preliminary Evaluation of Camptothecin Derivatives

作　　者：胡玉琦[1] 樊士勇[1] 史卫国[1] 仲伯华[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《解放军药学学报》2016年第3期211-214,共4页Pharmaceutical Journal of Chinese People's Liberation Army

摘　　要：目的为寻找生物利用度更好、抗肿瘤活性更高的喜树碱衍生物,设计新型喜树碱衍生物。方法对7-乙基-10-羟基喜树碱10位羟基进行化学结构修饰,连接生物相容性较好的羧基、特异性基团西佛碱结构,并对化合物进行体外细胞毒性评价。结果共合成11个未见文献报道的新化合物,其结构经1H-NMR及MS确证。体外细胞毒性评价表明:目标化合物对SPCA-1、MCF-79的体外细胞毒性大多强于阳性对照药物伊立替康。结论验证了西佛碱结构有助于提高喜树碱抗肿瘤活性。初步构效关系分析表明:羧烷基类化合物的活性随直链脂肪酸的增长而增强。Objective To design new camptothecin derivatives in order to discover the camptothecin derivatives of better bioavailability and higher anti-tumor activity. Methods Two series of eamptothecin derivatives were designed and synthesized by introducing biocompatible carboxyl groups and the schiff base structure to investi- gate their antitumor activities in vitro. Results There were eleven camptothecin derivatives synthesized. All the com- pounds were identified by 1H-NMR and MS. Most of the derivative compounds showed much greater anti-tumor activities against SPCA-1 and MCF-79 cell lines than irinotecan in vitro . Conclusion The schiff base structure has been proved to improve the anti-tumor activity of camptothecin. The anti-tumor activity of the carboxyalkyl class tar- get compound can be enhanced with the increased length of the fatty acid chain.

关 键 词：喜树碱衍生物 西佛碱 抗肿瘤 

分 类 号：R914.5[医药卫生—药物化学]