Synthesis of triazoloquinazolinone based compounds as tubulin polymerization inhibitors and vascular disrupting agents
Synthesis of triazoloquinazolinone based compounds as tubulin polymerization inhibitors and vascular disrupting agents
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DOI：
10.1016/j.ejmech.2016.03.056
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发表时间：
2016-06-10
影响因子：
6.7
通讯作者：
Lebegue, Nicolas
中科院分区：
文献类型：
--
作者：
Driowya, Mohsine;Leclercq, Julien;Lebegue, Nicolas
对一系列构象受限的CA4类似物1-phenyl-[1，2，4]triazolo[4，3-a]quinazolin-5-ones进行了微管蛋白聚合和生长抑制活性测试。3-羟基-4-甲氧基衍生物11d和12d是微管蛋白组装的有效抑制剂，但在一大批癌细胞系中，只有N-甲基化的12d具有有效的抗癌活性。经复方12d处理后，HUVECs发生明显的细胞形态改变，细胞迁移和管状形成，与血管损伤活性一致。(C)2016年爱思唯尔·马森SAS。版权所有。
A series of 1-phenyl-[1,2,4]triazolo[4,3-a]quinazolin-5-ones designed as conformationally restricted CA 4 analogues, were tested for their tubulin polymerization and growth inhibitory activities. The 3-hydroxy-4-methoxy derivatives 11d and 12d are potent inhibitors of tubulin assembly but only the N-methylated amid counterpart 12d possesses potent anticancer activity in a large panel of cancer cell lines. Upon treatment with compound 12d, remarkable cell shape changes as cell migration and tube formation were elicited in HUVECs, consistent with vasculature damaging activity. (C) 2016 Elsevier Masson SAS. All rights reserved.