2. Academic Validation
  3. Novel 3,4-seco bile acid diamides as selective anticancer proliferation and migration agents

Novel 3,4-seco bile acid diamides as selective anticancer proliferation and migration agents

  • Eur J Med Chem. 2016 Oct 21:122:574-583. doi: 10.1016/j.ejmech.2016.04.055.
Shi-Wei Mao 1,  Huang Chen 2,  Li-Fang Yu 1,  Fang Lv 2,  Ya-Jing Xing 2,  Ting Liu 1,  Jia Xie 2,  Jie Tang 3,  Zhengfang Yi 4,  Fan Yang 5
Affiliations

Affiliations

  • 1 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, 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 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China; Shanghai Key Laboratory of Green Chemistry and Chemical Processes, SCME, East China Normal University, Shanghai 200062, China.
  • 4 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: zfyi@bio.ecnu.edu.cn.
  • 5 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China. Electronic address: fyang@chem.ecnu.edu.cn.
PMID: 27448915 DOI: 10.1016/j.ejmech.2016.04.055
Abstract

A series of new seco-A ring bile acid diamides were synthesized, and their antiproliferative activities against PC3M (prostate), HT29 (colon) and ES-2 (ovarian) Cancer cell lines were investigated using SRB assays. Most synthesized compounds presented improved antiproliferative activities compared to the parent bile acids (IC50 > 80 μM), especially the piperazine conjugated compound 27 with IC50 values of 1.07, 4.58 and 3.86 μM against PC3M, HT29 and ES-2 Cancer cell lines, respectively. In addition, all the tested compounds showed less cytotoxic activity on a noncancerous cell line (HAF), and the most active compound 27 exhibited the highest selectivity (Selectivity Index, SI(PC3M) = 26.3). Furthermore, 27 could also enhance G1 arrest in PC3M cell, revealed by cell cycle analysis, and increase anti-migration activity on PC3M cells, confirmed by transwell migration assay.

Keywords

Anticancer; Antiproliferative activity; Cell cycle arrest; Migration; Seco A-ring bile acid diamide; Selectivity.

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