药学学报, 2013, 48(12): 1792-1799
引用本文:
周洁, 朱枝祥, 陈晓光, 徐柏玲. 氮杂吲哚类PARP-1抑制剂的合成及活性评价[J]. 药学学报, 2013, 48(12): 1792-1799.
ZHOU Jie, ZHU Zhi-xiang, CHEN Xiao-guang, XU Bai-ling. Synthesis and activity evaluation of PARP-1 inhibitors with azaindole skeleton[J]. Acta Pharmaceutica Sinica, 2013, 48(12): 1792-1799.

氮杂吲哚类PARP-1抑制剂的合成及活性评价
周洁, 朱枝祥, 陈晓光, 徐柏玲
中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 活性物质发现与适药化研究北京市重点实验室, 北京 100050
摘要:
PARP-1通过催化ADP-核糖单元(ADP-ribose)从烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD+)转移至各种底物蛋白上,参与损伤DNA的修复过程,是潜在的新机制的抗肿瘤药物靶标。本文设计合成了新结构氮杂吲哚类目标化合物16个,获得了对PARP-1具有抑制活性的化合物8个,其中2-位为脂环胺取代的氮杂吲哚对PARP-1和PARP-2均有抑制活性。
关键词:    PARP-1      抑制剂      氮杂吲哚      抗肿瘤药物     
Synthesis and activity evaluation of PARP-1 inhibitors with azaindole skeleton
ZHOU Jie, ZHU Zhi-xiang, CHEN Xiao-guang, XU Bai-ling
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
Abstract:
PARP[poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD+ to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.
Key words:    PARP-1    inhibitor    azaindole    antitumor agent   
收稿日期: 2013-07-12
基金项目: 中国医学科学院、北京协和医学院药物研究所基本科研业务费资助项目(2013CHX16).
通讯作者: 徐柏玲
Email: xubl@imm.ac.cn
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