Design and synthesis of novel Gefitinib analogues with improved anti-tumor activity.
Design and synthesis of novel Gefitinib analogues with improved anti-tumor activity.
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DOI：
10.1016/j.bmc.2010.04.046
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发表时间：
2010-06-01
影响因子：
3.5
通讯作者：
Xu, Liang
中科院分区：
文献类型：
--
作者：
Wu, Xiaoqing;Li, Mingdong;Qu, Yang;Tang, Wenhua;Zheng, Youguang;Lian, Jiqin;Ji, Min;Xu, Liang
迫切需要设计和开发具有改善的抗肿瘤活性的新的和更有效的EGFR抑制剂。在这里，我们描述了两个系列的4-苯并噻吩基氨基喹唑啉作为新的类似物的EGFR抑制剂吉非替尼的设计和合成。在6种人癌细胞系中检查了这些新型吉非替尼类似物的抗肿瘤活性。与母体Gefitinib相比，大多数新化合物显示出对癌细胞的细胞毒性显著增加。此外，在7位侧链含有甲基或乙基的几种系列B化合物是有效的泛RTK抑制剂。与母体吉非替尼相比，这类化合物中的两种代表性化合物15和17具有增强的体外抑制癌细胞生长和诱导细胞凋亡以及体内抑制具有高HER-2的人癌细胞中肿瘤形成的能力。因此，它们可能是有前途的先导化合物，可作为目前吉非替尼治疗或吉非替尼耐药患者的替代药物，可能通过同时阻断多种RTK信号通路。
There is an urgent need to design and develop new and more potent EGFR inhibitors with improved anti-tumor activity. Here we describe the design and synthesis of two series of 4-benzothienyl amino quinazolines as new analogues of the EGFR inhibitor Gefitinib. The anti-tumor activity of these novel Gefitinib analogues in 6 human cancer cell lines was examined. Compared with the parental Gefitinib, most of the new compounds show a markedly increased cytotoxicity to cancer cells. Furthermore, several of the series B compounds that side chains at position 7 contain either a methyl or ethyl group are potent pan-RTK inhibitors. Two representative compounds in this class, 15 and 17, have an enhanced capability to inhibit cancer cell growth and induce apoptosis in vitro and inhibit tumor formation in vivo in human cancer cells with high HER-2, as compared with the parental Gefitinib. Thus they may be promising lead compounds to be developed as an alternative for current Gefitinib therapy or for Gefitinb-resistant patients, potentially via simultaneously blocking multiple RTK signaling pathways.
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影响因子：
2.7
作者：
Petrov, Kimberly G.;Zhang, Yue-Mei;Lackey, Karen E.
通讯作者：
Lackey, Karen E.
影响因子：
158.5
作者：
Kobayashi, S;Boggon, TJ;Halmos, B
通讯作者：
Halmos, B
影响因子：
3.4
作者：
Telliez, Aurelie;Desroses, Matthieu;Henichart, Jean-Pierre
通讯作者：
Henichart, Jean-Pierre
microRNA miR-34抑制人类胰腺癌肿瘤发射细胞。
影响因子：
3.7
作者：
Ji Q;Hao X;Zhang M;Tang W;Yang M;Li L;Xiang D;Desano JT;Bommer GT;Fan D;Fearon ER;Lawrence TS;Xu L
通讯作者：
Xu L
影响因子：
7.3
作者：
REWCASTLE, GW;DENNY, WA;FRY, DW
通讯作者：
FRY, DW