研究简报

链霉菌CB03234-S中天赐霉素衍生物的发现

  • 薛露 ,
  • 张丽花 ,
  • 张成玉 ,
  • 赵鑫 ,
  • 党伟帆 ,
  • 王昭昕 ,
  • 王春华 ,
  • 所同川 ,
  • 颜晓晖
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  • a 天津中医药大学中医药研究院 天津 301617
    b 北京大学天然药物及仿生药物国家重点实验室 北京 100191
    c 天津中医药大学中药制药工程学院 天津 301617

收稿日期: 2021-11-10

  修回日期: 2021-12-09

  网络出版日期: 2021-12-31

基金资助

国家自然科学基金(81872779); 天然药物及仿生药物国家重点实验室开放基金(K202116)

Discovery of Tiancimycin Congeners from Streptomyces sp. CB03234-S

  • Lu Xue ,
  • Lihua Zhang ,
  • Chengyu Zhang ,
  • Xin Zhao ,
  • Weifan Dang ,
  • Zhaoxin Wang ,
  • Chunhua Wang ,
  • Tongchuan Suo ,
  • Xiaohui Yan
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  • a Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617
    b State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191
    c College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617

Received date: 2021-11-10

  Revised date: 2021-12-09

  Online published: 2021-12-31

Supported by

National Science Foundation of China(81872779); State Key Laboratory of Natural and Biomimetic Drugs(K202116)

摘要

天赐霉素是一种蒽醌骈合型烯二炔类化合物, 具有显著的抗肿瘤活性. 通过在天赐霉素A高产菌株放线菌CB03234-S中异源表达两个细胞色素P450羟化酶基因dynE10dynOrf19, 分离得到三个天赐霉素衍生物1~3. 通过一维和二维核磁共振、高分辨质谱和圆二色谱测定了它们的化学结构. 天赐霉素H (1)为天赐霉素D的C-9羟基化产物, TNM T1 (2)为一个烯二炔的环化产物, TNM T3 (3)为已知化合物. 化合物1对所有四种测试的肿瘤细胞株, 如HeLa细胞、MB49细胞、B16细胞和BIU87细胞均具有较强的抗肿瘤活性.

本文引用格式

薛露 , 张丽花 , 张成玉 , 赵鑫 , 党伟帆 , 王昭昕 , 王春华 , 所同川 , 颜晓晖 . 链霉菌CB03234-S中天赐霉素衍生物的发现[J]. 有机化学, 2022 , 42(4) : 1241 -1247 . DOI: 10.6023/cjoc202111018

Abstract

Tiancimycins (TNMs) are anthraquinone-fused enediynes with phenomenal antitumor activity. By heterologous expression of two cytochrome P450 hydroxylase genes, dynE10 and dynOrf19, in the TNMs high-producing strain Streptomyces sp. CB03234-S, three TNM derivatives 1~3 were isolated. Their chemical structures were determined by one-dimensional and two-dimensional NMR, high resolution mass spectrometry and circular dichroism. TNM H (1) is the C-9-hydroxylated product of TNM D, TNM T1 (2) is a cycloaromatized product, and TNM T3 (3) is a known compound. Compound 1 exhibited strong antitumor activity against the four tested cancer cell lines, including HeLa, MB49, B16 and BIU87.

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