Discovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP-ribose) polymerase-1/2 inhibitors
Discovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP-ribose) polymerase-1/2 inhibitors
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DOI：
10.1016/j.febslet.2005.01.036
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发表时间：
2005-02-28
期刊：
影响因子：
3.5
通讯作者：
Mutoh, S
中科院分区：
文献类型：
--
作者：
Iwashita, A;Hattori, K;Mutoh, S
两类喹唑啉酮衍生物和喹喔啉衍生物分别被鉴定为有效的和选择性的聚（ADP-核糖）聚合酶-1和2（PARP-1）和（PARP-2）抑制剂。在使用重组PARP-1和PARP-2的PARP酶测定中，喹唑啉酮衍生物对PARP-1显示出相对高的选择性，喹喔啉衍生物对PARP-2显示出上级选择性。通过X射线结构研究和同源性建模相结合的SBDD分析表明，抑制剂与PARP-1和PARP-2存在不同的相互作用。这些发现为设计PARP-1和PARP-2的选择性抑制剂提供了新的结构框架。(C)2005年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Two classes of quinazolinone derivatives and quinoxaline derivatives were identified as potent and selective poly(ADP-ribose) polymerase-1 and 2 (PARP-1) and (PARP-2) inhibitors, respectively. In PARP enzyme assays using recombinant PARP-1 and PARP-2, quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2. SBDD analysis via a combination of X-ray structural study and homology modeling suggested distinct interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new structural framework for the design of selective inhibitors for PARP-I and PARP-2. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.