Synthesis and antitumor activity evaluation of 4,6-disubstituted quinazoline derivatives as novel PI3K inhibitors
Synthesis and antitumor activity evaluation of 4,6-disubstituted quinazoline derivatives as novel PI3K inhibitors
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新型PI3K抑制剂4,6-二取代喹唑啉衍生物的合成及抗肿瘤活性评价
DOI：
10.1016/j.bmcl.2016.08.015
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发表时间：
2016-09-15
影响因子：
2.7
通讯作者：
Zhang, San-Qi
中科院分区：
文献类型：
--
作者：
Hei, Yuan-Yuan;Xin, Minhang;Zhang, San-Qi
设计并合成了一系列4,6-二取代喹唑啉衍生物作为PI3K抑制剂。所有化合物对HCT-116和MCF-7细胞株均表现出显著的抗增殖活性，其中化合物A7、A9和A11对HCT-116的抗增殖活性最强。进一步的PI3K抑制活性评价表明，化合物A7对PI3K酶具有较高的抑制活性。体内抗肿瘤实验表明，化合物A7能有效抑制S-180模型小鼠的肿瘤生长。这些结果表明，我们设计的化合物可以作为有效的PI3K抑制剂和有效的抗肿瘤药物。(C) 2016 Elsevier Ltd.版权所有。
A series of 4,6-disubstituted quinazoline derivatives as potential PI3K inhibitors were designed and synthesized. All compounds exhibited significant anti-proliferative activities against HCT-116 and MCF-7 cell lines, and compounds A7, A9, and A11 displayed the most potent anti-proliferative activity against the HCT-116. Further PI3K inhibitory activity evaluation showed that compound A7 displayed high potency against PI3K enzymes. The in vivo anti-tumor study showed compound A7 can efficaciously inhibit tumor growth in a mice S-180 model. These results suggest that our designed compounds can serve as potent PI3K inhibitors and effective antitumor agents. (C) 2016 Elsevier Ltd. All rights reserved.