Acridone derivatives: Design, synthesis, and inhibition of breast cancer resistance protein ABCG2
Acridone derivatives: Design, synthesis, and inhibition of breast cancer resistance protein ABCG2
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DOI：
10.1016/j.bmc.2007.02.017
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发表时间：
2007-04-15
影响因子：
3.5
通讯作者：
Di Pietro, Attilio
中科院分区：
文献类型：
--
作者：
Boumendjel, Ahcene;Macalou, Sira;Di Pietro, Attilio
乳腺癌耐药蛋白(BCRP，ABCG2)是最新发现的与MDR表型有关的ABC蛋白之一，目前对其抑制物知之甚少。在继续我们的旨在发现有效的多药耐药调节剂的计划中，我们构思并合成了新的吖啶酮类ABCG2抑制剂。目标分子的设计是基于早期用黄酮类和色酮类化合物抑制ABCG2的结果。利用人野生型(R482)ABCG2转基因细胞进行抑制性吖啶酮类化合物的合理筛选。介绍了目标化合物的合成、对ABCG2的抑制活性以及构效关系。其中一种吖啶酮甚至比参比抑制剂GF120918更有效，其抑制米托蒽醌外排的能力证明了这一点。(C)2007爱思唯尔有限公司。保留所有权利。
The breast cancer resistance protein (BCRP, ABCG2) is among the latest discovered ABC proteins to be involved in MDR phenotype and for which only few inhibitors are known. In continuing our program aimed at discovering efficient multidrug resistance modulators, we conceived and synthesized new acridones as ABCG2 inhibitors. The design of target molecules was based on earlier results dealing with ABCG2 inhibition with flavone and chromone derivatives. The human wild-type (R482) ABCG2-transfected cells were used for rational screening of inhibitory acridones. The synthesis of target compounds, the inhibitory activity against ABCG2, and structure-activity relationships are described. One of the acridones was even more potent than the reference inhibitor, GF120918, as shown by its ability to inhibit mitoxantrone efflux. (c) 2007 Elsevier Ltd. All rights reserved.