2. Academic Validation
  3. Synthesis of 3- and 29-substituted celastrol derivatives and structure-activity relationship studies of their cytotoxic activities

Synthesis of 3- and 29-substituted celastrol derivatives and structure-activity relationship studies of their cytotoxic activities

  • Bioorg Med Chem Lett. 2017 Aug 1;27(15):3450-3453. doi: 10.1016/j.bmcl.2017.05.083.
Wei-Guang Shan 1,  Han-Guang Wang 1,  Yan Chen 1,  Rui Wu 1,  Yan-Tao Wen 2,  Li-Wen Zhang 2,  You-Min Ying 1,  Jian-Wei Wang 1,  Zha-Jun Zhan 3
Affiliations

Affiliations

  • 1 College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, PR China.
  • 2 The Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, PR China.
  • 3 College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, PR China. Electronic address: zjnpr@zjut.edu.cn.
PMID: 28587825 DOI: 10.1016/j.bmcl.2017.05.083
Abstract

A series of 3-carbamate and 29-ester celastrol derivatives (compounds 1-26) were designed and synthesized. These analogues were evaluated for their cytotoxic activities against several Cancer cell lines. Cytotoxicity data revealed that the properties of substituents and substitution position had important influence on cytotoxic activity. Modification of C-3 hydroxyl with size-limited groups did not reduce the activity obviously. The introduction of polarity group like piperazine could improve the solubility. Compound 23 was chosen to further evaluate anti-tumor efficacy in vivo. It showed higher inhibition rate and better safety than celastrol during in vivo experiment by intragastric administration. The preliminary antitumor studies of compound 23in vivo showed that it might be promising for the development of new antitumor agents.

Keywords

C-3 hydroxyl derivatives; Celastrol; Cytotoxicity; In vivo activity; Intragastric administration.

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