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雷公藤红素抗肿瘤类衍生物研究进展

张雪玲, 李娜, 陈莉

张雪玲,李娜,陈莉. 雷公藤红素抗肿瘤类衍生物研究进展[J]. 中国药科大学学报,2024,55(6):826 − 836. DOI: 10.11665/j.issn.1000-5048.2023041802
引用本文: 张雪玲,李娜,陈莉. 雷公藤红素抗肿瘤类衍生物研究进展[J]. 中国药科大学学报,2024,55(6):826 − 836. DOI: 10.11665/j.issn.1000-5048.2023041802
ZHANG Xueling, LI Na, CHEN Li. Progress of research on celastrol derivatives as anti-tumor agents[J]. J China Pharm Univ, 2024, 55(6): 826 − 836. DOI: 10.11665/j.issn.1000-5048.2023041802
Citation: ZHANG Xueling, LI Na, CHEN Li. Progress of research on celastrol derivatives as anti-tumor agents[J]. J China Pharm Univ, 2024, 55(6): 826 − 836. DOI: 10.11665/j.issn.1000-5048.2023041802

雷公藤红素抗肿瘤类衍生物研究进展

基金项目: 国家自然科学基金项目(No.82104027);江苏省自然科学基金项目(BK20221523)
详细信息
    通讯作者:

    陈莉: Tel:13814083082 E-mail:chenli627@cpu.edu.cn

  • 中图分类号: R914

Progress of research on celastrol derivatives as anti-tumor agents

Funds: This study was supported by the National Natural Science Foundation of China (No.82104027);and the Natural Science Foundation of Jiangsu Province (BK20221523)
  • 摘要:

    雷公藤红素是从中药雷公藤Tripterygium wilfordii Hook.f.根皮中分离得到的五环三萜类化合物,可抑制多种恶性肿瘤的生长,但也存在毒性大、水溶性差、靶向性欠佳等缺陷。因此,对其进行结构修饰是近年来的研究热点。已报道的雷公藤红素结构修饰主要集中在C-20-COOH及AB环的C-2、C-3、C-6位或多位点同时优化。本文主要依据不同的修饰位点、修饰目的(提高Hsp90-Cdc37 PPI抑制作用等)和修饰手段(基于骈和原理和特定靶点等),综述近年来雷公藤红素抗肿瘤类衍生物的研究进展。此外,还简要讨论了衍生物的抗肿瘤活性、作用机制和构效关系,以期能够为发现新的高效、低毒、选择性强的CEL衍生物提供理论指导。

    Abstract:

    Celastrol, a pentacyclic triterpenoid compound derived from the root of Chinese herb Tripterygium wilfordii Hook.f.,can inhibit the growth of various types of malignant tumors. However, it still has some limitations, including high toxicity, poor water solubility, and low targeting efficiency. Therefore, structural modification of celastrol has become a research hotspot in recent years. The structural modifications of celstrol reported have focused on C-20-COOH and C-2, C-3, C-6 or multiple sites of AB ring. This review provides an overview of the research progress of anti-tumor celastrol derivatives in recent years according to different structural modification sites and purposes, such as enhancing the inhibitory effect on the Hsp90-Cdc37 protein-protein interaction, and modification methods, including principles of parallelism and targeting specific sites. In addition, it briefly discusses the antitumor activity, mechanism of action, and structure-activity relationship of these derivatives, aiming to provide theoretical guidance for the discovery of new celastrol derivatives with high efficiency, low toxicity, and strong selectivity.

  • 图  1   CEL-阿魏酸衍生物1~32的结构

    图  4   CEL-咪唑衍生物108~135的结构

    图  2   CEL-肉桂酸衍生物33~80的结构

    图  3   CEL-三氮唑衍生物81~107的结构

    图  5   CEL酯类和酰胺类衍生物136~158的结构

    图  6   CEL酯类衍生物159~173的结构

    图  7   CEL-NO供体衍生物174~184的结构

    图  8   CEL-噻唑烷二酮衍生物185~204的结构

    图  9   CEL C-20衍生物205~228的结构

    图  10   CEL-肉桂酰胺衍生物229~245的结构

    图  11   CEL-吡唑衍生物246~269的结构

    图  12   CEL-多肽衍生物270~280的结构

    图  13   CEL靶向Prdx1衍生物281~282的结构

    图  14   CEL C-20和C-3修饰衍生物283~313的结构

    图  15   CEL C-20衍生物329~343和C-3和C-20衍生物314~328的结构

    图  16   CEL多位点修饰衍生物344~364的结构

    图  17   CEL多位点修饰衍生物365~378的结构

    图  18   CEL多位点修饰衍生物379~405的结构

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出版历程
  • 收稿日期:  2023-04-17
  • 刊出日期:  2024-12-24

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