Antitumor properties of substituted (αE)-α-(1H-indol-3-ylmethylene)benzeneacetic acids or amides
Antitumor properties of substituted (αE)-α-(1H-indol-3-ylmethylene)benzeneacetic acids or amides
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DOI：
10.1016/j.bmc.2013.06.030
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发表时间：
2013-09-01
影响因子：
3.5
通讯作者：
Pittala, Valeria
中科院分区：
文献类型：
--
作者：
Forte, Giuseppe;Fortuna, Cosimo Gianluca;Pittala, Valeria
合成了一类新的吲哚衍生物，其特征在于（α-E）-α-（1H-吲哚-3-基亚甲基）苯乙酸或酰胺骨架。这些衍生物，测定对一组六种不同的肿瘤细胞系的细胞生长抑制活性，显示出强烈的抗增殖活性和选择性，主要是对DU 145细胞系。特别地，化合物2d-m和5因其细胞生长抑制活性而突出，并且其中，化合物2d因其相对于其他测试的肿瘤细胞系对DU 145的选择性而显现。DU 145用1 μ M的2d处理72 h后显示p21（Cip 1）诱导和Akt信号转导的抑制以及Rb的诱导。从计算的角度来看，使用两种不同的方法，以研究拓扑结构和电子性质的新化合物，并阐明其药物类似的性质。首先，拓扑和电子特征赋予最相关的生物活性的化合物进行了深化，在平行，一些ADME性质，如溶解性和渗透性进行了预测。(C)2013爱思唯尔有限公司保留所有权利。
A novel class of indole derivatives characterized by a (alpha E)-alpha-(1H-indo1-3-ylmethylene)benzeneacetic acid or amide scaffold was synthesized. These derivatives, assayed for cell-growth inhibition activity against a panel of six different tumor cell lines, showed strong antiproliferative activity and selectivity mainly towards DU145 cell line. In particular, compounds 2d-m and 5 stand out for their cell growth inhibitory activity and, among them, compound 2d emerged for its selectivity towards DU145 with respect to other tested tumor cell lines. DU145 treated with 1 mu M of 2d for 72 h showed p21(Cip1) induction and suppression of Akt signaling together with induction of Rb. From a computational point of view, two different approaches were used in order to study topology and electronic properties of the novel compounds and to shed light on their drug-likeness properties. Firstly, topological and electronic features of the compounds endowed with the most relevant biological activity were deepened; in parallel, some ADME properties like solubility and permeability were predicted. (C) 2013 Elsevier Ltd. All rights reserved.