Design, synthesis and in vitro antitumor activity of 4-aminoquinoline and 4-aminoquinazoline derivatives targeting EGFR tyrosine kinase
Design, synthesis and in vitro antitumor activity of 4-aminoquinoline and 4-aminoquinazoline derivatives targeting EGFR tyrosine kinase
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DOI：
10.1016/j.bmc.2008.07.038
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发表时间：
2008-08-15
影响因子：
3.5
通讯作者：
Shouman, Samia
中科院分区：
文献类型：
--
作者：
Abouzid, Khaled;Shouman, Samia
设计并合成了两个新的6-烷氧基-4-取代氨基喹唑啉类化合物（2-4f）及其生物等排喹啉同系物（5- 7 c）。通过将所设计的化合物对接到表皮生长因子受体（EGFR）的ATP结合位点进行虚拟筛选，预测这些化合物是否具有与EGFR抑制剂类似的结合模式。在EGFR高度表达的人乳腺癌细胞系（MCF-7）上对新合成的化合物进行体外测试。大多数测试化合物利用了IC 50值在纳摩尔范围内的有效抗肿瘤活性，特别是化合物3b，其在测试化合物中显示出最高活性，IC 50等于0.13 nmol。(C)2008爱思唯尔有限公司保留所有权利。
Two series of new 6-alkoxy-4-substituted-aminoquinazolines (2-4f) and their bioisoteric quinoline congeners (5-7c) were designed and synthesized. Virtual screening was carried out through docking the designed compounds into the ATP binding site of epidermal growth factor receptor (EGFR) to predict if these compounds have analogous binding mode to the EGFR inhibitors. The newly synthesized compounds were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. Most of the tested compounds exploited potent antitumor activity with IC50 values in the nanomolar range in particular compound 3b which displayed the highest activity among the tested compounds with IC50 equal to 0.13 nmol. (C) 2008 Elsevier Ltd. All rights reserved.