高等学校化学学报 ›› 2017, Vol. 38 ›› Issue (1): 47-55.doi: 10.7503/cjcu20160550

• 有机化学 • 上一篇    下一篇

微管菌素类似物的合成及抗肿瘤活性

白信法, 马宣, 解晓霞, 邵明莎, 郭宁宁, 严宁, 姚雷()   

  1. 烟台大学药学院, 新型制剂与生物技术药物研究山东省高校协同创新中心,分子药理和药物评价教育部重点实验室, 烟台 264005
  • 收稿日期:2016-07-29 出版日期:2017-01-10 发布日期:2016-10-31
  • 作者简介:联系人简介: 姚 雷, 男, 博士, 教授, 主要从事有机合成及天然产物全合成方面的研究. E-mail: yaoleiytu@163.com
  • 基金资助:
    烟台大学博士基金(批准号: YX13B04)和山东蓝色经济区人才发展项目(批准号: RS11YX)资助.

Synthesis and Anti-tumor Activity of Tubulysins Analogues

BAI Xinfa, MA Xuan, XIE Xiaoxia, SHAO Mingsha, GUO Ningning, YAN Ning, YAO Lei*()   

  1. Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs n Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005, China
  • Received:2016-07-29 Online:2017-01-10 Published:2016-10-31
  • Contact: YAO Lei E-mail:yaoleiytu@163.com
  • Supported by:
    † Supported by the Doctor Foundation of Yantai University, China(No.YX13B04) and the Talent Development Project of Blue Economic Zone of Shandong Province, China(No.RS11YX).

摘要:

以微管菌素为先导化合物, 设计合成了一系列类似物; 所有化合物的结构均经1H NMR, 13C NMR及HRMS确证, 均为新化合物. 采用噻唑蓝(MTT)法对其抗肿瘤活性进行了初步筛选, 结果表明, 化合物Ⅱb具有一定的抗肿瘤活性.

关键词: 微管菌素, 类似物, 抗肿瘤活性

Abstract:

Tubulysins family is a kind of natural compound with potent antitumor activity. To simplify the synthesis route and find new antitumor compounds is becoming a hotspot of research in recent years. Starting from 3-nitrobenzoic acid, after 7 steps transformations, 12 new tubulysin analogues were synthesized via the conformation restrain and bioisostere principle. These structures are featuring 3-substituted analine moieties. All these compounds are new compounds, and their structures were confirmed by 1H nuclear magnetic resonance(NMR), 13C NMR, and high resolution mass spectrometer(HRMS). The antitumor activities were tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyetl trazolium bromide(MTT) method in vitro using MDA-MB-231 and MCF7 cells, and compound Ⅱb exhibited moderate antitumor activity(7.6 and 11.8 μmol/L).

Key words: Tubulysins, Analogue, Antitumor activity

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