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

Bioorg Med Chem

Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-3915, FR CNRS INC3M, Université de Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, 5 rue Vaubénard, 14032 Caen Cedex, France.

Published: September 2008

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.

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http://dx.doi.org/10.1016/j.bmc.2008.07.046DOI Listing

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