Synthesis and antitumor activity evaluation of PI3K inhibitors containing 3-substituted quinazolin-4(3H)-one moiety

被引:21
作者
Zhang, Hao [1 ]
Xin, Min-Hang [1 ]
Xie, Xiao-Xiao [1 ]
Mao, Shuai [1 ]
Zuo, Sai-Jie [1 ]
Lu, She-Min [2 ]
Zhang, San-Qi [1 ]
机构
[1] Xi An Jiao Tong Univ, Sch Pharm, Dept Med Chem, Xian 710061, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Genet & Mol Biol, Xian 710061, Shaanxi, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
Quinazolin-4(3H)-ones; Synthesis; PI3K inhibitor; Antitumor activity; CLASS-I; ANTICANCER AGENTS; DISCOVERY; POTENT; NVP-BKM120; SERIES; TARGET; VITRO;
D O I
10.1016/j.bmc.2015.11.027
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In present study, a series of N-(2-methoxy-5-(3-substituted quinazolin-4(3H)-one-6-yl)-pyridin-3-yl) phenylsulfonamide were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against HCT116 and MCF-7 cancer cell lines. The SAR of title compounds was discussed. The compounds (S)-C5 and (S)-C8 displayed potent inhibitory activity against PI3Ks and mTOR, especially against PI3K alpha. In addition, compound (S)-C5 can efficaciously inhibit tumor growth in a mice S-180 model. These findings suggest that our designed compounds can serve as potent PI3K inhibitors and effective anticancer agents. (c) 2015 Published by Elsevier Ltd.
引用
收藏
页码:7765 / 7776
页数:12
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