English
往期目录
新闻公告
More
化学进展 前一篇   后一篇

• 综述与评论 •

吖啶类化合物在抗肿瘤方面的研究进展

郎许亮1,2, 栾旭东1,2, 高春梅*2,3, 蒋宇扬*1,2,3,4   

  1. 1. 清华大学化学系 北京 100084;
    2. 深圳市化学生物学重点实验室--省部共建国家重点实验室培育基地 深圳 518055;
    3. 清华大学深圳研究生院 深圳抗肿瘤创新药物研发与设计工程实验室 深圳 518055;
    4. 清华大学医学院 北京100084
  • 收稿日期:2011-11-01 修回日期:2012-04-01 出版日期:2012-08-24 发布日期:2012-08-06
  • 通讯作者: 高春梅, 蒋宇扬 E-mail:chunmeigao@sz.tsinghua.edu.cn; jiangyy@sz.tsinghua.edu.cn
  • 基金资助:

    国家自然科学基金项目(No.20902053)、国家高技术研究发展计划(863)项目(No.2012AA020305)、国家科技重大专项(No.2012ZX09506001-010)、国家重点基础研究发展 计划(973)项目(No.2012CB722605)和国家国际科技合作项目(No.2011DFA30620)资助

下载PDF ( 1049 ) 引用
导出 被引次数 ( 30 | 2 )

Recent Progress of Acridine Derivatives with Antitumor Activity

Lang Xuliang1,2, Luan Xudong1,2, Gao Chunmei2,3, Jiang Yuyang1,2,3,4   

  1. 1. Department of Chemistry, Tsinghua University, Beijing 100084, China;
    2. The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, Shenzhen 518055, China;
    3. Shenzhen Anti-Tumor Drug Development Engineering Laboratory, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China;
    4. School of Medicine, Tsinghua University, Beijing 100084, China
  • Received:2011-11-01 Revised:2012-04-01 Online:2012-08-24 Published:2012-08-06
吖啶类衍生物是一类含氮的有机杂环化合物,由于其在抗炎、抗菌及抗肿瘤方面体现了较好的生物活性而受到了广泛关注。本文对近年来吖啶类化合物在抗肿瘤方面的国内外研究成果进行了综述,对其主要作用靶点如端粒酶、拓扑异构酶Ⅰ/Ⅱ、微管蛋白、ABCG2/ P-glycoprotein (P-gP)以及蛋白激酶等方面的研究进行了介绍,并指出该类化合物的发展方向及应用前景。
关键词： 吖啶, 抗肿瘤, 靶点
Acridines are a series of heterocyclic compounds, which have been received intense interest and used as anti-inflammatory, antibacterial and antitumour agents. This paper reviews some recent progresses in the research of the antitumor activity of acridine derivatives, including as the inhibition of telomerase, topoisomerases Ⅰ and Ⅱ, tubulin, ABCG2/P-gP, protein kinases, etc. The prospects and potential applications of such acridine compounds are outlooked. Contents 1 Introduction
2 Antitumor activity of acridine derivatives
2.1 Telomerase inhibition
2.2 Topoisomerase inhibition
2.3 Tubulin inhibition
2.4 Protein-kinase inhibition
2.5 P-gP and ABCG2 inhibition
3 Conclusion and Prospects
Key words: acridine, antitumor, drug targets

中图分类号: 

()
[1] Belmont P, Constant J F, Demeunynck M. Chem. Soc. Rev., 2001, 30: 70-81
[2] Lagutschenkov A, Dopfer O. J. Mol. Spectrosc., 2011, 268: 66-77
[3] Cholewiński G, Dzierzbicka K, Koodziejczyk A M. Pharm. Rep., 2011, 63: 305-336
[4] Kaur J, Singh P. Expert Opin. Ther. Pat., 2011, 21:437-454
[5] 姚成才(Yao C C). 肿瘤防治研究(Cancer. Res. Prev. Tr.), 2004, 31 (1): 62-64
[6] Bilsland A E, Cairney C J, Nicol K W. J. Cell. Mol. Med., 2011, 15: 179-186
[7] Harley C B, Futcher A B, Greider C W. Nature, 1990, 345: 458-460
[8] Kelland L R. Eur. J. Cancer, 2005, 41: 971-979
[9] Neidle S. FEBS J., 2010, 277: 1118-1125
[10] Campbell N H, Parkinson G N, Reszka A P, Neidle S. J. Am. Chem. Soc., 2008, 130: 6722-6724
[11] Harrison R J, Gowan S M, Kelland L R, Neidle S. Bioorg. Med. Chem. Lett., 1999, 9: 2463-2468
[12] Harrison R J, Reszka A P, Haider S M, Romagnoli B, Morrell J, Read M A, Gowan S M, Incles C M, Kelland L R, Neidle S. Bioorg. Med. Chem. Lett., 2004, 14: 5845-5849
[13] Schultes C M, Guyen B, Cuesta J, Neidle S. Bioorg. Med. Chem. Lett., 2004, 14: 4347-4351
[14] Moore M J, Schultes C M, Cuesta J, Cuenca F, Gunaratnam M, Tanious F A, Wilson W D, Neidle S. J. Med. Chem., 2006, 49: 582-599
[15] Harrison R J, Cuesta J, Chessari G, Read M A, Basra S K, Reszka A P, Morrell J, Gowan S M, Incles C M, Tanious F A, Wilson W D, Kelland L R, Neidle S. J. Med. Chem., 2003, 46: 4463-4476
[16] Redman J E, Granadino-Roldán J M, Schouten J A, Ladame S, Reszka A P, Neidle S, Balasubramanian S. Org. Biomol. Chem., 2009, 7: 76-84
[17] Sparapani S, Haider S M, Doria F, Gunaratnam M, Neidle S. J. Am. Chem. Soc., 2010, 132: 12263-12272
[18] Fu Y T, Keppler B R, Soares J, Jarstfer M B. Bioorg. Med. Chem., 2009, 17: 2030-2037
[19] Baumann P, Podell E, Cech T R. Mol. Cell. Biol., 2002, 22: 8079-8087
[20] Laronze-Cochard M, Kim Y M, Brassart B, Riou J F, Laronze J Y, Sapi J. Eur. J. Med. Chem., 2009, 44: 3880-3888
[21] Carole D, Michel D, Julien C, Florence D, Anna N, Severine J, Gerard D, Pierre T D, Jean-Pierre G. Bioorg. Med. Chem., 2005, 13: 5560-5568
[22] Tan J H, Ou T M, Hou J Q, Lu Y J, Huang S L, Luo H B, Wu J Y, Huang Z S, Wong K Y, Gu L Q. J. Med. Chem., 2009, 52: 2825-2835
[23] Arola A, Vilar R. Curr. Top. Med. Chem., 2008, 8: 1405-1415
[24] Wang J. J. Mol. Biol., 1971, 55: 523-533
[25] Froelichammon S J, Gale K C, Osheroff N. J. Biol. Chem., 1994, 269: 7719-7725
[26] 黄兆琦(Huang Z Q). 医学研究生学报(J. Postgrad. Med.), 2002, 15 (6): 539-541
[27] Denny W. Med. Chem. Rev., 2004, 1: 257-266
[28] Blasiak J, Gloc E, Drezowski J, Wozniak K, Zadrozny M, Skorski T, Pertynski T. Mutat. Res., 2003, 535: 25-34
[29] Su T L, Chou T C, Kim J Y, Huang J T, Ciszewska G, Ren W Y, Otter G M, Sirotnak F M, Watanabe K A. J. Med. Chem., 1995, 38: 3226-3235
[30] Chang J Y, Lin C F, Pan W Y, Bacherikov V, Chou T C, Chen C H, Dong H J, Cheng S Y, Tasi T J, Lin Y W, Chen K T, Chen L T, Su T L. Bioorg. Med. Chem., 2003, 11: 4959-4969
[31] Bacherikov V A, Chang J Y, Lin Y W, Chen C H, Pan W Y, Dong H, Lee R Z, Chou T C, Su T L. Bioorg. Med. Chem., 2005, 13: 6513-6520
[32] Chen C H, Lin Y W, Zhang X, Chou T C, Tsai T J, Kapuriya N, Kakadiya R, Su T L. Eur. J. Med. Chem., 2009, 44: 3056-3059
[33] Oppegard L, Ougolkov A, Luchini D, Schoon R, Goodell J, Kaur H, Billadeau D, Ferguson D, Hiasa H. Eur. J. Pharmacol., 2009, 602: 223-229
[34] Capranico G, Marinello J, Baranello L. Biochim. Biophys. Acta, 2010, 1806: 240-250
[35] Gao C M, Liu F, Luan X D, Tan C Y, Liu H X, Xie Y H, Jin Y B, Jiang Y Y. Bioorg. Med. Chem., 2010, 18: 7507-7514
[36] Luan X D, Gao C M, Sun Q S, Tan C Y, Liu H X, Jin Y B, Jiang Y Y. Chem. Lett., 2011, 40: 728-729
[37] Atwell G, Cain B, Baguley B, Finlay G, Denny W. J. Med. Chem., 1984, 27: 1481-1485
[38] Adams A, Guss J, Collyer C, Denny W, Wakelin L. Biochemistry, 1999, 38: 9221-9233
[39] Denny W A, Baguley B C. Curr. Top. Med. Chem., 2003, 3: 339-353
[40] Schneider E, Darkin S J, Lawson P A, Ching L M, Ralph R K, Baguley B C. Eur. J. Canc. Clin. Oncol., 1988, 24: 1783-1790
[41] Dittrich C, Coudert B, Paz-Ares L, Caponigro F, Salzberg M, Gamucci T, Paoletti X, Hermans C, Lacombe D, Fumoleau P. Eur. J. Cancer, 2003, 39: 330-334
[42] Twelves C. Ann. Oncol., 2002, 13: 777-780
[43] Spicer J A, Gamage S A, Atwell G J, Finlay G J, Baguley B C, Denny W A. J. Med. Chem., 1997, 40: 1919-1929
[44] Deady L W, Rodemann T, Zhuang L, Baguley B C, Denny W A. J. Med. Chem., 2003, 46: 1049-1054
[45] Deady L W, Rogers M L, Zhuang L, Baguley B C, Denny W A. Bioorg. Med. Chem., 2005, 13: 1341-1355
[46] Bu X Y, Chen J J, Deady L W, Smith C L, Baguley B C, Greenhalgh D, Yang S J, Denny W A. Bioorg. Med. Chem., 2005, 13: 3657-3665
[47] Jordan M A, Wilson L. Nat. Rev. Cancer, 2004, 4: 253-265
[48] Gerlach M, Claus E, Baasner S, Müller G, Polymeropoulos E, Schmidt P, Günther E, Engel J. Arch. Pharm., 2004, 337: 695-703
[49] Zuse A, Schmidt P, Baasner S, Böhm K J, Müller K, Gerlach M, Günther E G, Unger E, Prinz H. J. Med. Chem., 2007, 50: 6059-6066
[50] Swinney D C, Anthony J. Nat. Rev. Drug Discov., 2011, 10: 507-519
[51] Sharma P S, Sharma R, Tyagi R. Curr. Cancer Drug Tar., 2008, 8: 53-75
[52] Huwe A, Mazitschek R, Giannis A. Angew. Chem. Int. Ed., 2003, 42: 2122-2138
[53] Cuny G D, Robin M, Ulyanova N P, Patnaik D, Pique V, Casano G, Liu J F, Lin X, Xian J, Glicksman M A. Bioorg. Med. Chem. Lett., 2010, 20: 3491-3494
[54] Xu W C, Zhou Q, Ashendel C L, Chang C T, Chang C J. Bioorg. Med. Chem. Lett., 1999, 9: 2279-2282
[55] Chen Q P, Deady L W, Polya G H. Bio. Chem. Hoppe-Seyler, 1994, 375: 223-235
[56] Hannun Y, Bell R M. J. Biol. Chem., 1988, 263: 5124-5131
[57] Qi Q, He K, Yoo M H, Chan C B, Liu X, Zhang Z, Olson J J, Xiao G, Wang L, Mao H. J. Biol. Chem., 2012, 287: 6112-6127
[58] Luan X D, Gao C M, Zhang N N, Chen Y Z, Sun Q S, Tan C Y, Liu H X, Jin Y B, Jiang Y Y. Bioorg. Med. Chem., 2011, 19: 3312-3319
[59] Vlaming M L, Lagas J S, Schinkel A H. Adv. Drug Delivery Rev., 2009, 61: 14-25
[60] Van Loevezijn A, Allen J D, Schinkel A H, Koomen G J. Bioorg. Med. Chem. Lett., 2001, 11: 29-32
[61] Hyafil F, Vergely C, Du V P, Grand-Perret T. Cancer Res., 1993, 53: 4595-4602
[62] Boumendjel A, Macalou S, Ahmed-Belkacem A, Blanc M, di Pietro A. Bioorg. Med. Chem., 2007, 15: 2892-2897
[63] Gopinath V S, Thimmaiah P, Thimmaiah K N. Bioorg. Med. Chem., 2008, 16: 474-487
[64] Hegde R, Thimmaiah P, Yerigeri M C, Krishnegowda G, Thimmaiah K N, Houghton P J. Eur. J. Med. Chem., 2004, 39: 161-177
[65] Singh P, Kaur J, Yadav B, Komath S S. Bioorg. Med. Chem., 2009, 17: 3973-3979
[66] Singh P, Kaur J, Yadav B, Komath S S. Bioorg. Med. Chem., 2010, 18: 4212-4223
[67] Rethy B, Hohmann J, Minorics R, Varga A, Ocsovszki I, Molnar J, Juhasz K, Falkay G, Zupko I. Anticancer Res., 2008, 28: 2737-2743
[1] 顾顺心, 姜琴, 施鹏飞. 发光铱(Ⅲ)配合物抗肿瘤活性研究及应用[J]. 化学进展, 2022, 34(9): 1957-1971.
[2] 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.
[3] 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.
[4] 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.
[5] 谭晓晓, 李国帅, 王庆鹏, 王炳全, 李大成, 王鹏. 作为抗肿瘤药物的小分子四价铂[J]. 化学进展, 2018, 30(6): 831-846.
[6] 何良, 谭彩萍, 曹乾, 毛宗万. 磷光环金属化铱(Ⅲ)配合物在癌症治疗方面的应用[J]. 化学进展, 2018, 30(10): 1548-1556.
[7] 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.
[8] 郑小辉, 夏立新, 毛宗万. 基于核酸修饰新策略的抗肿瘤铂配合物设计[J]. 化学进展, 2016, 28(7): 1029-1038.
[9] 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.
[10] 李思迪, 侯信, 亓洪昭, 赵瑾, 原续波. 外泌体:为高效药物投递策略提供天然的内源性纳米载体[J]. 化学进展, 2016, 28(2/3): 353-362.
[11] 王家敏, 史蕾, 刘海洋. 咔咯及其金属配合物与DNA的作用和抗肿瘤活性[J]. 化学进展, 2015, 27(6): 755-762.
[12] 李晓晖*, 黄美玲, 刘丽娜, 王燕云. 环肽类组蛋白去乙酰化酶抑制剂[J]. 化学进展, 2014, 26(09): 1527-1536.
[13] 黎燕, 黄卫, 黄平, 朱新远, 颜德岳. 抗肿瘤药物输送系统[J]. 化学进展, 2014, 26(08): 1395-1408.
[14] 崔建国, 刘亮, 甘春芳, 肖琦, 黄燕敏. 芳（杂）环甾体化合物的合成及生理活性研究[J]. 化学进展, 2014, 26(0203): 320-333.
[15] 任天斌, 侠文娟, 吴畏, 李永勇*. 刺激响应型聚合物前药[J]. 化学进展, 2013, 25(05): 775-784.