Mitotic Arrest Induced by a Novel Family of DNA Topoisomerase II Inhibitors

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• 作者：Leticia G. Len ; Carla Ros-Luci ; David Tejedor ; Eduardo Prez-Roth ; Juan C. Montero ; Atanasio Pandiella ; Fernando Garca-Tellado ; Jos M. Padrn
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：May 13, 2010
• 年：2010
• 卷：53
• 期：9
• 页码：3835-3839
• 全文大小：781K
• 年卷期：v.53,no.9(May 13, 2010)
• ISSN：1520-4804

文摘

A small structure-focused library of propargylic enol ethers was prepared by means of a modular and efficient chemodifferentiating organocatalyzed multicomponent reaction. The most active compound (GI₅₀ 0.25 μM) against solid tumor cells was selected as lead. Cell cycle analysis and immunoblotting demonstrated arrest at the metaphase, pointing out human topoisomerase II as plausible molecular target. In vitro assays were carried out, showing that the lead behaves as a catalytic inhibitor of the enzyme.