English
新闻公告
More
化学进展 2013, Vol. 25 Issue (04): 545-554 DOI: 10.7536/PC120820 前一篇   后一篇

所属专题: 酶化学

• 金属与核酸 •

DNA拓扑异构酶抑制剂

杜可杰, 王忆, 梁捷雯, 计亮年, 巢晖*   

  1. 中山大学化学与化学工程学院 生物无机与合成化学教育部重点实验室 广州 510275
  • 收稿日期:2012-08-01 修回日期:2012-11-01 出版日期:2013-04-24 发布日期:2013-04-09
  • 通讯作者: 巢晖 E-mail:ceschh@mail.sysu.edu.cn
  • 基金资助:

    国家自然科学基金项目(No. 21071155, 21172273, 21171177);教育部高校博士点基金博导类课题(No. 20110171110013)和广东省自然科学基金团队项目(No.9351027501000003)资助

DNA Topoisomerase Inhibitors

Du Kejie, Wang Yi, Liang Jiewen, Ji Liangnian, Chao Hui*   

  1. School of Chemistry and Chemical Engineering, MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Sun Yat-sen University, Guangzhou 510275, China
  • Received:2012-08-01 Revised:2012-11-01 Online:2013-04-24 Published:2013-04-09

DNA拓扑异构酶是一种广泛存在于真核细胞和原核细胞中的重要生物酶,对DNA转录、复制、染色体分离及基因表达等过程中的DNA拓扑结构起着重要的调控作用。研究发现,与正常细胞不同,DNA拓扑异构酶在肿瘤细胞中表现出不受其他因素影响的高水平表达,而许多抗肿瘤药物的作用机制也与DNA拓扑异构酶密切相关,因此它作为抗肿瘤药物的重要靶点引起了研究者的广泛关注。本文对DNA拓扑异构酶的结构、分类及生物功能进行了简要的归纳,总结了近年来DNA拓扑异构酶抑制剂的研究进展,并重点对金属配合物作为DNA拓扑异构酶抑制剂的研究现状进行了详细的介绍。

DNA topoisomerases (Topo) are ubiquitous enzymes in eukaryotic cell and prokaryotic cell. They are crucial for cellular genetic processes, such as replication, recombination, transcription, chromosome condensation, and the maintenance of genome stability by catalyzing the passage of individual DNA strands (topoisomerase Ⅰ) or double helices (topoisomerase Ⅱ) through one another. In accordance, topoisomerases are over expressed in cancer cell growth and thus are important cellular targets for anticancer drugs. The structures and biological functions of topoisomerases are discussed in this review. Moreover, some recent progresses of organic compounds and metal complexes as DNA topoisomerase inhibitors are discussed in detail.

Contents
1 Introduction
2 Structures and mechanisms of DNA topoisomerases
2.1 Structures of DNA topoisomerases
2.2 Mechanisms of DNA topoisomerases
3 Biological functions of DNA topoisomerases
3.1 Regulation of topological states of DNA
3.2 Role of DNA topoisomerases in recombination and repair
4 DNA topoisomerases inhibitors
4.1 Mechanisms of DNA topoisomerase inhibition
4.2 Organic compounds as DNA topoisomerase inhibitors
4.3 Metal complexes as DNA topoisomerase inhibitors
5 Perpective

中图分类号: 

()

[1] Prommer Y. DNA Topoisomerases and Cancer, 1st Edition. Springer, 2012
[2] Wang J C. J. Mol. Biol., 1971, 55: 523-533
[3] Wang J C. Ann. Rev. Biochem., 1985, 54: 665-697
[4] Li T K, Liu L F. Annu. Rev. Pharmacol. Toxicol., 2001, 41: 53-77
[5] Lima C D, Wang J C, Mondragon A. Nature, 1994, 367: 138-146
[6] Redinbo M R, Stewart L, Kuhn P, Champoux J J, Hol W G J. Science, 1998, 279: 1504-1513
[7] Juan C C, Hwang J, Liu A A, Whang P J, Knutsen T, Huebner K, Croce C M, Zhang H, Wang J C, Liu L F. Proc. Natl. Acad. Sci., 1988, 85: 8910-8913
[8] Feinberg H, Changela A, Mondragon A. Nat. Struct. Biol., 1999, 6: 961-968
[9] Champoux J J. Annu. Rev. Biochem., 2001, 70: 369-413
[10] Pflugfelder M T, Liu L F, Liu A A, Tewey K M, Peng J W, Knutsen T, Huebner K, Croce C M, Wang J C. Proc. Natl. Acad. Sci. U. S. A., 1988, 85: 7177-7181
[11] Tan K B, Dorman T E, Falls K M, Chung T D Y, Mirabelli C K, Crooke S T, Mao J. Cancer Res., 1992, 52: 231-234
[12] Classen S, Olland S, Berger J M. Proc. Natl. Acad. Sci. U. S. A., 2003, 100: 10629-10634
[13] Heck M M, Earnshaw W C. J. Cell Biol., 1986, 103: 2569-2581
[14] Lyu Y L, Lin C P, Azarova A M, Cai L, Wang J C, Liu L F. Mol. Cell Biol., 2006, 26: 7929-7941
[15] McClendon A K, Gentry A C, Dickey J S, Brinch M, Bendsen S, Andersen A H, Osheroff N. Biochemistry, 2008, 47: 13169-13178
[16] Chen S J, Wang J C. J. Biol. Chem., 1998, 273: 6050-6056
[17] Berger J M, Gamblin S J, Harrison S C, Wang J C. Nature, 1996, 379: 225-232
[18] Lee M P, Sander M, Hsieh T S J. Biol. Chem., 1989, 264: 13510-13518
[19] Deweese J E, Osheroff N. Biochemistry, 2009, 48: 1439-1441
[20] Dong K C, Berger J M. Nature, 2007, 450: 1201-1205
[21] Gellert M, Mizuuehi K, O' Dea M H, Nash H A. Proc. Natl. Acad. Sci. U. S. A., 1976, 73: 3872-3876
[22] Wang J C. Nat. Rev. Mol. Cell Biol., 2002, 3: 430-440
[23] Abdurashidova G, Radulescu S, Sandoval O, Zahariev S, Danailov M B, Demidovich A, Santamaria L, Biamonti G, Riva S, Falaschi A. EMBO J., 2007, 26: 998-1009
[24] McClendon A K, Rodriguez A C, Osheroff N. J. Biol. Chem., 2005, 280: 39337-39345
[25] Fachinetti D, Bermejo R, Cocito A, Minardi S, Katou Y, Kanoh Y, Shirahige K, Azvolinsky A, Zakian V A, Foiani M. Mol. Cell, 2010, 39: 595-605
[26] Wu H Y, Shyy S H, Wang J C, Liu L F. Cell, 1988, 53: 433-440
[27] Drolet M, Phoenix P, Menzel R, Massé E, Liu L F, Crouch R J. Proc. Natl. Acad. Sci. U. S. A., 1995, 92: 3526-3530
[28] Tuduri S, Crabbé L, Conti C, Tourrière H, Holtgreve-Grez H, Jauch A, Pantesco V, de Vos J, Thomas A, Theillet C, Pommier Y, Tazi J, Coquelle A, Pasero P. Nat. Cell Biol., 2009, 11: 1315-1324
[29] Lotito L, Russo A, Chillemi G, Bueno S, Cavalieri D, Capranico G. J. Mol. Biol., 2008, 377: 311-322
[30] Ju B G, Lunyak V V, Perissi V, Garcia-Bassets I, Rose D W, Glass C K, Rosenfeld M G. Science, 2006, 312: 1798-1802
[31] Vos S M, Tretter E M, Schmidt B H, Berger J M. Nat. Rev. Mol. Cell Biol., 2011, 12: 827-841
[32] Neale M J, Pan J, Keeney S. Nature, 2005, 436: 1053-1057
[33] Keeney S. Genome Dyn. Stab., 2008, 2: 81-123
[34] Harmon F G, Brockman J P, Kowalczykowski S C. J. Biol. Chem., 2003, 278: 42668-42678
[35] Cejka P, Cannavo E, Polaczek P, Masuda-Sasa T, Pokharel S, Campbell J L, Kowalczykowski S C. Nature, 2010, 467: 112-116
[36] MacDonald T L, Labroli M A, Tepe J J. Comprehensive Natural Products Chemistry, 2010, 7: 593-614
[37] Pommier Y. Chem. Rev., 2009, 109: 2894-2902
[38] Froelich-Ammon S J, Osheroff N. J. Biol. Chem., 1995, 270: 21429-21432
[39] Pommier Y. Nat. Rev. Cancer, 2006, 6: 789-802
[40] Cline S D, Macdonald T L, Osheroff N. Biochemistry, 1997, 36: 13095-13101
[41] Larsen A K, Escargueil A E, Skladanowski A. Pharmacology Therapeutics, 2003, 99: 167-181
[42] Wall M E, Wani M C. Cancer Res., 1995, 55: 753-760
[43] Cheng K, Rahier N J, Eisenhauer B M, Gao R, Thomas S J, Hecht S M. J. Am. Chem. Soc., 2005, 127: 838-839
[44] Song Y, Shao Z, Dexheimer T S, Scher E S, Pommier Y, Cushman M. J. Med. Chem., 2010, 53: 1979-1989
[45] Sheng C Q, Miao Z Y, Zhang W N. Curr. Med. Chem., 2011, 18: 4389-4409
[46] Bonner W M, Redon C E, Dickey J S, Nakamura A J, Sedelnikova O A, Solier S, Pommier Y. Nat. Rev. Cancer, 2008, 8: 957-967
[47] Long B H, Rose W C, Vyas D M, Matson J A, Forenza S. Curr. Med. Chem. Anticancer Agents, 2002, 2: 255-266
[48] 蒙凌华(Meng L H), 张永炜(Zhang Y W), 丁健(Ding J). 中国新药杂志(Chinese Journal of New Drugs), 2002, 9: 675-683
[49] Pommier Y, Leo E, Zhang H L, Marchand C. Chemistry & Biology, 2010, 17: 421-433
[50] Bonner J A, Kozelsky T F. Cancer Chemother. Pharmacol., 1996, 39: 109-112
[51] Azarova A M, Lyu Y, Lin C, Tsai Y, Lau J Y, Wang J C, Liu L F. Proc. Natl. Acad. Sci. U. S. A., 2007, 107: 11014-11019
[52] Salerno S, Da Settimo F, Taliani S, Simorini F, La Motta C, Fornaciari G, Marini A M. Curr. Med. Chem., 2010, 17: 4270-4290
[53] 陈禹(Chen Y), 杜可杰(Du K J), 巢晖(Chao H), 计亮年(Ji L N). 化学进展(Prog. Chem.), 2009, 21: 836-844
[54] Van Waardenburg R C, De Jong L A, Van Eijndhoven M A, Verseyden C, Pluim D, Jansen L E, Bjornsti M A, Schellens J H. J. Biol. Chem., 2004, 279: 54502-54509
[55] Lo Y C, Ko T P, Su W C, Su T L, Wang A H J. J. Inorg. Biochem., 2009, 103: 1082-1092
[56] Wang P, Leung C H, Ma D L, Lu W, Che C M. Chem. Asian J., 2010, 5: 2271-2280
[57] Liu J, Leung C H, Chow A L, Sun R W, Yan S C, Che C M. Chem. Commun., 2011, 719-721
[58] Gopal V Y N, Jayaraju D, Kondapi A K. Biochemistry, 1999, 38: 4382-4388
[59] Gao F, Chao H, Wang J Q, Yuan Y X, Sun B, Wei Y F, Peng B, Ji L N. J. Biol. Inorg. Chem., 2007, 12: 1015-1027
[60] Gao F, Chao H, Zhou F, Chen X, Wei Y F, Ji L N. J. Inorg. Biochem., 2008, 102: 1050-1059
[61] Chen X, Gao F, Zhou Z X, Yang W Y, Guo L T, Ji L N. J. Inorg. Biochem., 2010, 104: 576-582
[62] Du K J, Wang J Q, Kou J F, Li G Y, Wang L L, Chao H, Ji L N. Eur. J. Med. Chem., 2011, 46: 1056-1065
[63] Kou J F, Qian C, Wang J Q, Chen X, Wang L L, Chao H, Ji L N. J. Biol. Inorg. Chem., 2012, 17: 81-96
[64] Beckford F, Thessing J, Woods J, Didion J, Gerasimchuk N, Sarrias A G, Seeramc N P. Metallomics, 2011, 3: 491-502
[65] Yan J J, Chow A L F, Leung C H, Sun R W Y, Ma D L, Che C M. Chem. Commun., 2010, 3893-3895
[66] Castelli S, Vassallo O, Katkar P, Che C M, Sun R W, Desideri A. Arch. Biochem. Biophys., 2011, 516: 108-112
[67] Sun R W Y, Li C K L, Ma D L, Yan J J, Lok C N, Leung C H, Zhu N Y, Che C M. Chem. Eur. J., 2010, 16: 3097-3113
[68] Miller M C, Stineman C N, Vance J R, West D X, Hall I H. Appl. Organometal. Chem., 1999, 13: 9-19
[69] Zeglis B M, Divilov V, Lewis J S. J. Med. Chem., 2011, 54: 2391-2398
[70] Seng H L, Von S T, Tan K W, Maah M J, Ng S W, Rahman R N, Caracelli I, Ng C H. Biometals, 2010, 23: 99-118
[71] Liu Y C, Chen Z F, Liu L M, Peng Y, Hong X, Yang B, Liu H G, Liang H, Orvig C. Dalton Trans., 2009, 48: 10813-10823
[72] Rupesh K R, Deepalatha S, Krishnaveni M, Venkatesan R, Jayachandran S. Eur. J. Med. Chem., 2006, 41: 1494-1503

[1] 张婷婷, 洪兴枝, 高慧, 任颖, 贾建峰, 武海顺. 基于铜金属有机配合物的热活化延迟荧光材料[J]. 化学进展, 2022, 34(2): 411-433.
[2] 朱泉霏, 郝俊迪, 严靖雯, 王雨, 冯钰锜. FAHFAs:生物功能、分析及合成[J]. 化学进展, 2021, 33(7): 1115-1125.
[3] 颜高杰, 吴琼, 谈玲华. 富氮唑类金属配合物的设计合成及应用[J]. 化学进展, 2021, 33(4): 689-712.
[4] 郭文迪, 刘晔. 过渡金属配合物催化炔烃和亲核试剂的羰化反应[J]. 化学进展, 2021, 33(4): 512-523.
[5] 王欣瑜, 赵富平, 张儒, 孙子茹, 刘胜男, 高清志. 抗肿瘤缺氧诱导因子-1的小分子抑制剂[J]. 化学进展, 2021, 33(12): 2259-2269.
[6] 谢嘉恩, 罗雨珩, 张黔玲, 张平玉. 金属配合物在双光子荧光探针中的应用研究[J]. 化学进展, 2021, 33(1): 111-123.
[7] 孙子茹, 刘胜男, 高清志. 靶向葡萄糖转运蛋白(GLUTs)抗癌药物的开发[J]. 化学进展, 2020, 32(12): 1869-1878.
[8] 牟泽怀, 王银军, 谢鸿雁. 稀土金属配合物催化芳香型乙烯基极性单体立构选择性聚合[J]. 化学进展, 2020, 32(12): 1885-1894.
[9] 周中高, 元洋洋, 徐国海, 陈正旺, 李梅. 糖基氮杂环卡宾及其过渡金属配合物的合成与催化性能[J]. 化学进展, 2019, 31(2/3): 351-367.
[10] 袁世芳, 闫艺. 同核双金属烯烃聚合催化剂[J]. 化学进展, 2019, 31(12): 1737-1748.
[11] 徐子悦, 张运昌, 林佳乐, 王辉, 张丹维, 黎占亭. 药物输送体系构筑中的超分子组装策略[J]. 化学进展, 2019, 31(11): 1540-1549.
[12] 李享, 石家愿, 邱爽, 王明芳, 刘长林*. SOD1抑制与活性氧信号转导的调控[J]. 化学进展, 2018, 30(10): 1475-1486.
[13] 邱康强, 朱宏翊, 计亮年, 巢晖. 金属配合物用于细胞内动态实时荧光示踪研究[J]. 化学进展, 2018, 30(10): 1524-1533.
[14] 孙悦文, 金素星, 王晓勇, 郭子建. 金属配合物在肿瘤化学免疫治疗中的应用前景[J]. 化学进展, 2018, 30(10): 1573-1583.
[15] 叶霁青, 岳晓虹, 孙丽萍. 小分子IL-6/STAT3信号通路抑制剂[J]. 化学进展, 2016, 28(7): 1099-1111.
阅读次数
全文


摘要

DNA拓扑异构酶抑制剂