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多样取代的吡咯并[2,3-a]咔唑的合成、Pim 激酶抑制活性和体外抗增殖活性。

Synthesis, Pim kinase inhibitory potencies and in vitro antiproliferative activities of diversely substituted pyrrolo[2,3-a]carbazoles.

机构信息

Clermont Université, Université Blaise Pascal, SEESIB, BP10448, F-63000 Clermont-Ferrand, France.

出版信息

Bioorg Med Chem. 2010 Sep 15;18(18):6865-73. doi: 10.1016/j.bmc.2010.07.036. Epub 2010 Aug 19.

Abstract

The synthesis of new pyrrolo[2,3-a]carbazole derivatives diversely substituted at the C-6 to C-9 positions is described. These compounds were tested for their kinase inhibitory potencies toward three kinases (Pim-1, Pim-2, Pim-3) as well as for their in vitro antiproliferative activities toward a human fibroblast primary culture and three human solid cancer cell lines (PC3, DU145, and PA 1). Moreover, molecular docking studies were performed to explain the enhanced inhibitory activity of the most active compound 3d.

摘要

描述了新型吡咯并[2,3-a]咔唑衍生物的合成,这些化合物在 C-6 到 C-9 位具有不同取代基。测试了这些化合物对三种激酶(Pim-1、Pim-2、Pim-3)的激酶抑制活性以及对人成纤维细胞原代培养和三种人实体癌细胞系(PC3、DU145 和 PA1)的体外增殖活性。此外,还进行了分子对接研究,以解释最活性化合物 3d 的增强抑制活性。

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