Design, synthesis and biological evaluation of C6-modified celastrol derivatives as potential antitumor agents

Kaiyong Tang; Qingqing Huang; Jafeng Zeng; Guangming Wu; Jinwen Huang; Junfang Pan; Wei Lu

doi:10.3390/molecules190710177

Design, synthesis and biological evaluation of C6-modified celastrol derivatives as potential antitumor agents

Molecules. 2014 Jul 14;19(7):10177-88. doi: 10.3390/molecules190710177.

Authors

Kaiyong Tang¹, Qingqing Huang², Jafeng Zeng³, Guangming Wu⁴, Jinwen Huang⁵, Junfang Pan⁶, Wei Lu⁷

Affiliations

¹ Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, China. tangkaiyong@huatuodrug.com.
² Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, China. qqhuang@sat.ecnu.edu.cn.
³ Shanghai Hotmed Sciences Co., Ltd., Shanghai 201201, China. zengjiafeng@huatuodrug.com.
⁴ Shanghai Hotmed Sciences Co., Ltd., Shanghai 201201, China. wuguangming@huatuodrug.com.
⁵ Shanghai Hotmed Sciences Co., Ltd., Shanghai 201201, China. huangjinwen@hotmail.com.
⁶ Shanghai Hotmed Sciences Co., Ltd., Shanghai 201201, China.
⁷ Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, China. wlu@chem.ecnu.edu.cn.

Abstract

New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468). The results showed that most of the compounds displayed potent inhibition against BGC823, H4, and Bel7402, with IC50s of 1.84-0.39 μM. The best compound NST001A was tested in an in vivo antitumor assay on nude mice bearing Colo 205 xenografts, and showed significant inhibition of tumor growth at low concentrations. Therefore, celastrol C-6 derivatives are potential drug candidates for treating cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents* / chemical synthesis
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Hep G2 Cells
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasms, Experimental / drug therapy*
Neoplasms, Experimental / pathology
Pentacyclic Triterpenes
Triterpenes / chemical synthesis
Triterpenes / chemistry
Triterpenes / pharmacology*
Xenograft Model Antitumor Assays*

Substances

Antineoplastic Agents
Pentacyclic Triterpenes
Triterpenes
celastrol