具有对人癌细胞系抗增殖和促凋亡作用的新型石胆酸和鹅去氧胆酸哌嗪基羧酰胺。
New lithocholic and chenodeoxycholic piperazinylcarboxamides with antiproliferative and pro-apoptotic effects on human cancer cell lines.
作者信息
El Kihel Laïla, Clément Monique, Bazin Marc-Antoine, Descamps Géraldine, Khalid Mohamed, Rault Sylvain
机构信息
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.
出版信息
Bioorg Med Chem. 2008 Sep 15;16(18):8737-44. doi: 10.1016/j.bmc.2008.07.046. Epub 2008 Jul 23.
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.
合成了六种新的合成胆汁酸衍生物，并在体外针对各种人类癌细胞（多形性胶质母细胞瘤（GBM）、多发性骨髓瘤（KMS - 11）和结肠癌细胞系（HCT - 116））进行了测试。化合物IIIb对多发性骨髓瘤细胞表现出最佳活性（半数致死剂量（LD(50)）：8.5±0.5微摩尔）。这种活性与Mcl - 1和PARP - 1的切割、NFκB信号传导的抑制以及DNA片段化有关，表明存在凋亡细胞死亡信号通路。
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