3-取代的7-苯基-吡咯并喹啉酮在人癌细胞系中显示出强大的细胞毒性活性。

3-substituted 7-phenyl-pyrroloquinolinones show potent cytotoxic activity in human cancer cell lines.

作者信息

Gasparotto Venusia, Castagliuolo Ignazio, Ferlin Maria Grazia

机构信息

Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Italy.

出版信息

J Med Chem. 2007 Nov 1;50(22):5509-13. doi: 10.1021/jm070534b. Epub 2007 Oct 4.

DOI:10.1021/jm070534b

PMID:17915851

Abstract

A novel series of 3-alkyl-substituted 7-phenyl-3H-pyrrolo[3,2-f]quinolin-9-ones (7-PPyQs) was synthesized with the aim to optimize the cytotoxic activity of recently identified PPyQs, promising inhibitors of tubulin polymerization. All compounds inhibited the growth of 11 human tumor cell lines at submicromolar concentrations as well as two human resistant cancer sublines, A549-T12 and A549-T24. FACS analysis indicated that all compounds caused significant arrest of the A549 cell cycle in G2/M phase at 0.1 and 1 muM and a good correlation between the cytotoxicity IC50 and their ability to block the cell cycle was observed.

摘要

合成了一系列新型的3-烷基取代的7-苯基-3H-吡咯并[3,2-f]喹啉-9-酮（7-PPyQs），目的是优化最近鉴定出的PPyQs的细胞毒性活性，PPyQs是微管蛋白聚合的有前景的抑制剂。所有化合物在亚微摩尔浓度下均抑制11种人类肿瘤细胞系以及两种人类耐药癌症亚系A549-T12和A549-T24的生长。流式细胞术分析表明，所有化合物在0.1和1μM时均导致A549细胞周期在G2/M期显著停滞，并且观察到细胞毒性IC50与其阻断细胞周期的能力之间具有良好的相关性。