有机化学 ›› 2014, Vol. 34 ›› Issue (1): 155-160.DOI: 10.6023/cjoc201307049Z 上一篇    下一篇

研究论文

10-羟基喜树碱氨基酸缀合物的合成及抗肿瘤活性研究

孟光荣a, 李嘉俊a, 王国林b, 董孟杰b, 张倩a   

  1. a 复旦大学药学院药物化学教研室 上海 201203;
    b 浙江大学附属一院PET中心 杭州 310003
  • 收稿日期:2013-08-04 修回日期:2013-08-30 出版日期:2014-01-25 发布日期:2013-09-17
  • 通讯作者: 张倩 E-mail:zhangqian511@shmu.edu.cn
  • 基金资助:

    国家自然科学基金(No. 30870730)资助项目.

Synthesis and Cytotoxic Activities of the Amino Acid-Conjugates of 10-Hydroxycamptothecin

Meng Guangronga, Li Jiajuna, Wang Guolinb, Dong Mengjieb, Zhang Qiana   

  1. a Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203;
    b Positron Emission Tomography Center, First Affiliated Hospital, Zhejiang University, Hangzhou 310003
  • Received:2013-08-04 Revised:2013-08-30 Online:2014-01-25 Published:2013-09-17
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 30870730).

以10-羟基喜树碱为原料,通过两碳边链链接,合成了一系列10-羟基喜树碱氨基酸缀合物和9-硝基-10-羟基喜树碱氨基酸缀合物. 采用CCK-8法测试了合成化合物体外对人口腔鳞癌细胞KB、人肝癌细胞HepG2和小鼠结肠癌细胞C26三组细胞株的增殖抑制活性,结果表明部分目标化合物对所选肿瘤细胞株显示了潜在的抑制活性,其中10-羟基喜树碱氨基酸缀合物的体外活性明显优于9-硝基-10-羟基喜树碱氨基酸缀合物的体外活性.

关键词: 喜树碱, 氨基酸缀合物, 抗肿瘤活性

A series of amino acid-conjugates of 10-hydroxycamptothecin and 9-nitro-10-hydroxycamptothecin were synthesized by means of a two-carbon side chain from 10-hydroxycamptothecin. The cytotoxic activities of all the synthetic compounds on KB, HepG2 and C26 in vitro were evaluated by CCK-8 assay. The results revealed that part of the conjugates exhibit potent anti-proliferative activities against selected tumor cell lines. Among them, the amino acid-conjugates of 10-hydroxycamptothecin show more potent activities than those of 9-nitro-10-hydroxycamptothecin in vitro as antitumor agents.

Key words: camptothecin, amino acid-conjugates, cytotoxic activities