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
  • 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: [email protected].
  • 5. Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, SCME, East China Normal University, Shanghai 200062, China. Electronic address: [email protected].
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.