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

被引：40

作者：

El Kihel, Laila ^{[1
]}

Clement, Monique ^{[2
]}

Bazin, Marc-Antoine ^{[1
]}

Descamps, Geraldine ^{[2
]}

Khalid, Mohamed ^{[3
]}

Rault, Sylvain ^{[1
]}

机构：

[1] Univ Caen Basse Normandie, Ctr Etud & Rech Medicament Normandie, FR CNRS INC3M, UFR Sci Pharmaceut,UPRES EA3915, F-14032 Caen, France

[2] CHU Nantes, Inst Biol, INSERM, U601, F-44093 Nantes, France

[3] Univ Hassan Premier, Fac Sci & Tech, Settat 26000, Morocco

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 18期

关键词：

steroid-heterocycle; bile acid derivatives; apoptosis; anticancer; multiple myeloma;

D O I：

10.1016/j.bmc.2008.07.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (LD50: 8.5 +/- 0.5 mu M). This activity was associated with Mcl-1 and PARP-1 cleavage, inhibition of NF kappa B signaling, and DNA fragmentation, demonstrating an apoptotic cell death signaling pathway. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：8737 / 8744

页数：8

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