Design, synthesis and biological evaluation of novel c-Met/HDAC dual inhibitors

被引：13
|
作者：
Dong, Yuhong [1 ]
Hu, Hao [1 ]
Sun, Yuwei [1 ]
Qin, Mingze [1 ]
Gong, Ping [1 ]
Hou, Yunlei [1 ]
Zhao, Yanfang [1 ]
机构：
[1] Shenyang Pharmaceut Univ, Key Lab Struct Based Drug Design & Discovery, Minist Educ, 103 Wenhua Rd, Shenyang 110016, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 23期
基金：
中国国家自然科学基金;
关键词：
c-Met; HDAC; Design; Synthesis; Antitumor activity; HISTONE DEACETYLASE INHIBITORS; 4-PHENOXYQUINOLINE DERIVATIVES; MULTITARGET THERAPEUTICS; MULTIPLE LIGANDS; CANCER; MET; POLYPHARMACOLOGY; RECEPTOR; MOIETY;
D O I：
10.1016/j.bmcl.2020.127610
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
In this work three novel series of c-Met/HDAC bifunctional inhibitors were designed and synthesized by merging pharmacophores of c-Met and HDAC inhibitors. The most potent compound 11j inhibited c-Met kinase and HDAC1 with IC50 values of 21.44 and 45.22 nM, respectively. In addition, 11j showed efficient antiproliferative activities against both MCF-7 and A549 cells with greater potency than the reference drug SAHA and Cabozantinib. This work may lay the foundation for developing novel dual c-Met/HDAC inhibitors as potential anticancer therapeutics.
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页数：7
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