β'-羟基-α,β-不饱和酮：一种用于抗癌药物设计的新药效基团。第2部分。

beta'-Hydroxy-alpha,beta-unsaturated ketones: A new pharmacophore for the design of anticancer drugs. Part 2.

作者信息

León Leticia G, Carballo Rubén M, Vega-Hernández María C, Miranda Pedro O, Martín Víctor S, Padrón Juan I, Padrón José M

机构信息

Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Universidad de la Laguna, C/ Astrofísico Francisco Sánchez, 2, 38206 La Laguna, Spain.

出版信息

ChemMedChem. 2008 Nov;3(11):1740-7. doi: 10.1002/cmdc.200800212.

DOI:10.1002/cmdc.200800212

PMID:18846591

Abstract

Novel antiproliferative beta'-acyloxy-alpha,beta-unsaturated ketones were obtained by means of an iron(III)-catalyzed multicomponent domino process (ABB' 3CR). The most active derivatives displayed GI(50) values in the range of 0.5-3.9 muM against a panel of representative human solid tumor cell lines: A2780, SW1573, HBL-100, T-47D and WiDr. Analysis of cells following 24 h exposure to these drugs showed cell cycle arrest in the S and G(2)/M phase, in a dose-dependent manner. Our data indicate that the beta'-acyloxy-alpha,beta-unsaturated ketones cause permanent damage to the cells and induce apoptosis.

摘要

通过铁（III）催化的多组分多米诺过程（ABB' 3CR）获得了新型抗增殖β'-酰氧基-α，β-不饱和酮。最具活性的衍生物对一组代表性人类实体瘤细胞系：A2780、SW1573、HBL-100、T-47D和WiDr的GI(50)值在0.5-3.9 μM范围内。在暴露于这些药物24小时后对细胞进行分析，结果显示细胞周期在S期和G(2)/M期呈剂量依赖性停滞。我们的数据表明，β'-酰氧基-α，β-不饱和酮会对细胞造成永久性损伤并诱导细胞凋亡。