European Journal of Medicinal Chemistry p. 372 - 381 (2017)
Update date:2022-08-05
Topics:
Cui, Zhishan
Chen, Shaopeng
Wang, Yanwei
Gao, Chunmei
Chen, Yuzong
Tan, Chunyan
Jiang, Yuyang
Overexpression of EGFR is often associated with advanced stage disease and poor prognosis. In certain cancers, Src works synergistically with EGFR to promote proliferation, survival, invasion and metastasis. Development of dual-target drugs against EGFR and Src is of therapeutic advantage against these cancers. Based on molecular docking and our previous studies, we rationally designed a new series of azaacridine derivatives as potent EGFR and Src dual inhibitors. Most of the synthesized azaacridines displayed good antiproliferative activity against K562 and A549?cells. The representative compound 13b showed nM IC50 values against K562 and A549?cells, and inhibited EGFR at inhibition rate of 33.53% at 10?μM and Src at inhibition rate of 72.12% at 1?μM. Furthermore, compound 13b could inhibit the expression of EGFR, p-EGFR, Src and p-Src. Moreover, 13b efficiently inhibited the invasion of tumor cells and induced cancer cells apoptosis. Our study suggested that azaacridine scaffold can be developed as novel multi-target kinase inhibitors for cancer therapy.
View MoreWuxi Morality Chemical Co., Ltd(expird)
Contact:
Address:B/7F, 321th WuYun Rd, Wanda Plaza, Wuxi City, 214174, China
Contact:+852-8198 2399
Address:9E, Leapont Industrial Building, 18-28 Wo Liu Hang Road, Shatin, New Territories, Hong Kong
Hangzhou Yanshan Chemical Co.,Ltd.
Contact:86-571- 87698076
Address:Room 1001, #1 Building, Zhongtian MCC, No.2 Youzhinong, Wenyi West Road, Xihu District, Hangzhou, China
Zhengzhou Yuanli Biological Technology Co., Ltd.
Contact:+86-371-67897870/67897895
Address:No. 38, Qingyang Street, Zhengzhou, Henan, China
Xiamen Huasing Chemicals Co.Ltd.
Contact:0086-592-6228397
Address:NO.24, Xinglin North 2nd Road,Jimei district
Doi:10.1016/S0040-4039(01)93016-3
(1981)Doi:10.1002/chem.201605520
(2017)Doi:10.1002/aoc.3565
(2017)Doi:10.1016/S0040-4039(01)87454-2
(1971)Doi:10.1021/jo001276s
(2001)Doi:10.1021/ja01475a028
(1961)