The synthesis and antitumor activity of lithocholic acid and its derivatives

Xiao-Long He; Yajing Xing; Xiang-Zhong Gu; Jie-Xin Xiao; Ying-Ying Wang; Zhengfang Yi; Wen-Wei Qiu

doi:10.1016/j.steroids.2017.06.009

The synthesis and antitumor activity of lithocholic acid and its derivatives

Steroids. 2017 Sep:125:54-60. doi: 10.1016/j.steroids.2017.06.009. Epub 2017 Jun 23.

Authors

Xiao-Long He¹, Yajing Xing², Xiang-Zhong Gu³, Jie-Xin Xiao¹, Ying-Ying Wang¹, Zhengfang Yi², Wen-Wei Qiu⁴

Affiliations

¹ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Chemical Engineering, East China Normal University, Shanghai 200241, China.
² Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
³ Department of Research and Development, Jiangsu Jiaerke Pharmaceuticals Group Co Ltd., Zhenglu Town, Changzhou 213111, China.
⁴ Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Chemical Engineering, East China Normal University, Shanghai 200241, China. Electronic address: wwqiu@chem.ecnu.edu.cn.

PMID: 28648585
DOI: 10.1016/j.steroids.2017.06.009

Abstract

In this paper, a new and concise synthetic route of lithocholic acid (LCA) using commercially available steroid source deoxycholic acid is reported. A series of amide derivatives of LCA were also synthesized and investigated for their activity against the growth of MCF-7 and MCF-7/ADR cells using the sulforhodamine B assay. For MCF-7, the most potent compound 20 showed a 20-fold higher antitumor activity than LCA. For MCF-7/ADR, the most potent compound 24 showed a 22-fold higher antitumor activity than LCA. The transwell migration assay of 20 was evaluated on MDA-MB-231 cells. The colony formation and apoptosis assays of 20 were performed on MCF-7 and MCF-7/ADR cell lines.

Keywords: Antitumor; Apoptosis; Breast cancer; Lithocholic acid; Migration.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Movement / drug effects
Cell Proliferation / drug effects
Chemistry Techniques, Synthetic
Drug Screening Assays, Antitumor
Humans
Lithocholic Acid / chemical synthesis*
Lithocholic Acid / chemistry
Lithocholic Acid / pharmacology*
MCF-7 Cells
Structure-Activity Relationship

Substances

Antineoplastic Agents
Lithocholic Acid