Synthesis of polyhalo 2-aryl-4-aminoquinazolines and 3-amino-indazoles as anti-cancer agents
Synthesis of polyhalo 2-aryl-4-aminoquinazolines and 3-amino-indazoles as anti-cancer agents
复制标题
抗癌剂多卤代2-芳基-4-氨基喹唑啉和3-氨基吲唑的合成
DOI：
10.1039/c3ra23059g
复制
发表时间：
2013-01-01
期刊：
影响因子：
3.9
通讯作者：
Lin, Jun
中科院分区：
文献类型：
--
作者：
Yan, Sheng-Jiao;Dong, Ying;Lin, Jun
在碱性条件下，以聚环异邻苯二腈1a-1c与脒类盐酸反应制备了一系列聚环2-芳基-4-氨基喹唑啉3a-3n，收率达70-93%。并通过多环异苯二腈1a-1c与肼反应得到了收率为70-87%的新型多环3-氨基茚唑5和7。化合物3、5和7对人SKOV-3、HeLa、U2-OS、A549和MCF-7的体外抗肿瘤活性进行了评价。部分化合物表现出良好的生长抑制活性，其中3a是最有效的衍生物，对5种肿瘤细胞系的IC50值低于3.86 μ g mL（-1）。研究了代表性化合物5b在HCT116结直肠癌细胞系中的作用机制。结果表明，5b对肿瘤细胞活力的降低具有时间和浓度依赖性。经5b处理的细胞在细胞周期的G2/M期积累，最终进入凋亡。
A series of polyhalo 2-aryl-4-aminoquinazolines 3a-3n were prepared by reacting polyhalo isophthalonitriles 1a-1c with amidine hydrochlorides under basic conditions with good yields (70-93%). Also, through the reaction of polyhalo isophthalonitriles 1a-1c with hydrazines to give novel polyhalo 3-aminoindazoles 5 and 7 with moderate yield (70-87%). The anticancer activities of compounds 3, 5 and 7 were evaluated in vitro against human cell lines SKOV-3, HeLa, U2-OS, A549, and MCF-7. Some compounds showed excellent growth inhibitory activities and 3a was found to be the most potent derivative, with an IC50 value lower than 3.86 mu g mL(-1) against the five tumor cell lines. The mechanism of action of representative compound 5b was investigated in the HCT116 colorectal cancer cell line. It was shown that 5b reduced cell viability of cancer cells in a time and concentration dependent manner. Cells treated with 5b accumulate in the G2/M phase of the cell cycle and finally go into apoptosis.