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

• Novel 3,4-seco bile acid amides were designed and synthesized as anticancer agents.
• Most compounds displayed more antiproliferative activity than bile acids.
• 16 showed specific antiproliferative activity against ES-2 (IC50 = 3.11 μM; SI = 20).
• 27 (IC50 = 1.07 μM; SI = 26.3) inhibited colony forming and induced cell cycle arrest.
• 27 significantly inhibited migration of PC3M cells in a dose-dependent manner.

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, SIPC3M = 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.

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