Synthesis and evaluation of new thiourea derivatives as antitumor and antiangiogenic agents

被引：28
作者：
Bai, Wenjing [1 ,2 ]
Ji, Jianxin [1 ]
Huang, Qiang [4 ]
Wei, Wei [3 ]
机构：
[1] Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[3] Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China
[4] Zunyi Med Univ, Sch Pharm, Dept Clin Pharm, Zunyi 563000, Guizhou, Peoples R China
来源：
TETRAHEDRON LETTERS | 2020年 / 61卷 / 40期
关键词：
Thiourea derivatives; Antitumor; Antiangiogenesis; RTK inhibitors; MULTIKINASE INHIBITOR; ANGIOGENESIS; SORAFENIB; GROWTH; DESIGN; DISCOVERY; CARCINOMA; PATHWAYS; INVASION; VEGF;
D O I：
10.1016/j.tetlet.2020.152366
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
A series of novel thiourea derivatives were synthesized and evaluated by biological activities. Among them, compound 10e containing 3,5-bis(trifluoromethyl)phenyl moiety (R-1) at the terminal thiourea and phenylamino (R-2) at the terminal acyl position showed the best cytotoxic activities against seven cancer cell lines (NCI-H460, Colo-205, HCT116, MDA-MB-231, MCF-7, HepG2, PLC/PRF/5) and HUVECs. Moreover, compound 10e moderately inhibited various RTKs such as VEGFR2, VEGFR3, and PDGFR beta. Notably, 10e exhibited much better inhibitory effect of tumor formation and antiangiogenic activities than Sorafenib and Regorafenib at the same concentration. Further docking studies suggested that 10e could serve as potential candidate for cancer therapy. (C) 2020 Elsevier Ltd. All rights reserved.
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