Bioorganic & Medicinal Chemistry 2008-09-15

New lithocholic and chenodeoxycholic piperazinylcarboxamides with antiproliferative and pro-apoptotic effects on human cancer cell lines.

Laïla El Kihel, Monique Clément, Marc-Antoine Bazin, Géraldine Descamps, Mohamed Khalid, Sylvain Rault

Index: Bioorg. Med. Chem. 16 , 8737-44, (2008)

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Abstract

Six new synthetic bile acid derivatives were synthesized and tested in vitro against various human cancer cells (glioblastoma multiforme (GBM), multiple myeloma (KMS-11), and colonic carcinoma (HCT-116) cell lines. The best activity was obtained with compound IIIb on multiple myeloma cells (LD(50): 8.5+/-0.5 microM). This activity was associated with Mcl-1 and PARP-1 cleavage, inhibition of NFkappaB signaling, and DNA fragmentation, demonstrating an apoptotic cell death signaling pathway.