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化学进展 2008, Vol. 20 Issue (0203): 368-374 前一篇   后一篇

• 综述与评论 •

吲哚咔唑类化合物及其衍生物的抗肿瘤活性

陈苏婷 尤启冬*   

  1. (中国药科大学药物化学教研室 南京 210009)

  • 收稿日期:2007-04-16 修回日期:2007-07-24 出版日期:2008-03-24 发布日期:2008-03-24
  • 通讯作者: 尤启冬
下载PDF ( 1810 ) 引用
导出 被引次数 ( 41 | 4 )

Anticancer Activity of Indolocarbazoles

Chen Suting; You Qidong*

  

  1. ( Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China)
  • Received:2007-04-16 Revised:2007-07-24 Online:2008-03-24 Published:2008-03-24
  • Contact: You Qidong
吲哚咔唑类化合物是一类提取自微生物发酵液中的生物碱.这一类化合物及其衍生物如staurosporine、ED-110、NB-506、rebeccamycin、氮杂吲哚咔唑、吲哚咔唑糖缀合物、双吲哚马来酰亚胺等，被认为存在广泛的抗肿瘤作用靶点，包括多种与细胞周期有关的激酶、细胞核拓扑异构酶、与肿瘤细胞生长或凋亡相关的酶等。现已知，吲哚咔唑化合物是拓扑异构酶的致毒剂，其对蛋白激酶的抑制作用表现为竞争结合其ATP口袋上特异的氨基酸基团，从而抑制酶的活性，并引起细胞生长静止于G1期。多年来研究者们努力寻找此类化合物的良好结构，以期得到抗肿瘤活性提高的选择性激酶抑制剂。本文综述了吲哚咔唑类化合物的研究进展、临床应用、抗肿瘤活性产生的机制以及化合物的构效关系（SAR）等。
关键词： 吲哚咔唑, 拓扑异构酶, 蛋白激酶, DNA-拓扑异构酶I复合物, cyclin-CDK复合物, 构效关系

Indolocarbazole is a certain kind of alkaloid extracted by microbe fermentation. These compound, including their derivatives, such as staurosporine, ED-11, NB-506, rebeccamycin, azaindolocarbazole, indolocarbazole glycosides and bisindolylmaleimides, can act on many targets to exert anticancer function. It is now known that indolocarbazoles are effective topoisomerase poisons，and that they also inhibit protein kinases by competitively combining to special amino acid groups of the ATP pocket, which later causes the cell arrest in the G1 phase. During the recent years, researchers endeavored to look for better forms of these chemicals to act as selective inhibitors with improved anticancer activity. This review will mainly discuss the research progress, clinical applications, anticancer activity mechanism, and their structure-activity relationship (SAR) of indolocarbazole derivatives.

Key words: indolocarbazoles, topoisomerases, protein kinases, DNA-Topo I complex, cyclin-CDK complex, structure-activity relationship(SAR)

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