English
往期目录
新闻公告
More
化学进展 2009, Vol. 21 Issue (05): 845-855 前一篇   后一篇

• 金属药物专辑 •

金属抗癌药物设计的新策略和新趋势*

王晓勇1; 郭子建2**   

  1. （1.医药生物技术国家重点实验室  南京大学生命科学学院   南京 210093；2.配位化学国家重点实验室   南京大学化学化工学院   南京 210093）
  • 收稿日期:2009-02-17 修回日期:2009-01-27 出版日期:2009-05-24 发布日期:2009-05-05
  • 通讯作者: 郭子建 E-mail:zguo@nju.edu.cn
  • 基金资助:

    国家自然科学基金

下载PDF ( 3571 ) 引用
导出

New Strategies and Trends for the Design of Metal-Based Anticancer Drugs

Wang Xiaoyong1;  Guo Zijian2**   

  1. (1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China; 2. State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China)
  • Received:2009-02-17 Revised:2009-01-27 Online:2009-05-24 Published:2009-05-05
  • Contact: Guo Zijian E-mail:zguo@nju.edu.cn

金属药物有许多其它药物无法比拟的独特性质，以顺铂为代表的铂类抗癌药物在癌症临床化疗中发挥了巨大作用。但是铂类药物的毒副作用严重限制了它们的实际疗效和适用范围，因此需要继续研究具有不同作用机理的新型金属抗癌药物，以改良或补充现有铂类药物的性能。本文重点介绍了近年来设计金属抗癌药物的一些新策略，包括改变铂类药物与DNA的作用模式、改进铂类药物对肿瘤的靶向性、研发非铂类金属抗癌药物和寻找DNA以外的作用靶标等。这些内容体现了该领域的最新发展趋势，为从事金属抗癌药物开发研究的科技人员提供了有益的参考信息。

关键词： 金属配合物, 抗癌药物, 毒副反应, 设计策略

Metal-based anticancer agents have many unique properties that are superior to those of other drugs. As a representative of platinum anticancer drugs, cisplatin plays a crucial role in the treatment of various cancers in clinical chemotherapy. However, the actual efficacy and applicability of this sort of drugs have been greatly limited by their severe toxic side-effects. In order to mend the defects of current platinum drugs, it is necessary to develop novel metal-based anticancer agents with different mechanism of action. In this review, some new strategies for the design of metal-based anticancer drugs are discussed. These include (1) altering the interaction mode of platinum drugs with DNA, (2) enhancing the tumor-targeting property of platinum drugs, (3) developing non-platinum metal-based anticancer drugs, and (4) exploring new potential biological targets other than DNA. All these respects reflect the major trends in this field, which provide some valuable information for researchers pursuing new metal-based anticancer agents.

Contents
1 Introduction
2 Alteration of the reaction mode with DNA
3 Improvement in the targeting property of drugs
4 Development of non-platinum metal-based anticancer drugs
5 Exploration of non-classical targets
6 Conclusion

Key words: metal complexes, anticancer drugs, toxic side-effects, design strategy

中图分类号: 

()

[ 1 ] 　Kelland L. Nature Rev. Cancer , 2007 , 7 : 573 —584
[ 2 ] 　Galanski M, Jakupec M A , Keppler B K. Curr. Med. Chem. ,2005 , 12 : 2075 —2094
[ 3 ] 　Hambley T W. Dalton Trans. , 2007 , 4929 —4937
[ 4 ] 　Gielen M, Tiekink E R T. Metallotherapeutic Drugs and Metal-based Diagnostic Agents -the Use of Metals in Medicine. Chichester : John Wiley &Sons , Ltd. , 2005
[ 5 ] 　Pérez J M, Fuertes M A , Alonso C. Metal Compounds in Cancer Chemotherapy. Kerala : Research Signpost , 2005
[ 6 ] 　Momekov G, Momekova D. Expert . Opin. Ther. Patents , 2006 ,16 : 1383 —1403
[ 7 ] 　Bruijnincx P C A , Sadler P J . Curr. Opin. Chem. Biol . , 2008 ,12 : 197 —206
[ 8 ] 　Argyriou A A , Polychronopoulos P , Iconomou G, et al . Cancer Treat . Rev. , 2008 , 34 : 368 —377
[ 9 ] 　McWhinney S R , Goldberg RM, McLeod HL. Mol . Cancer Ther. ,2009 , 8 : 10 —16
[10 ] 　Pasetto L M, D’Andrea M R , Rossi E , et al . Crit . Rev. Oncol .Hemat . , 2006 , 59 : 159 —168
[11 ] 　Rabik C A , Dolan M E. Cancer Treat . Rev. , 2007 , 33 : 9 —23
[12 ] 　Wang X Y, Guo Z J . Anti-Cancer Agents Med. Chem. , 2007 , 7 :19 —34
[13 ] 　Kalinowska-Lis U , Ochocki J , Matlawska-Wasowska K. Coord.Chem. Rev. , 2008 , 252 : 1328 —1345
[14 ] 　Abu-Surrah A S. Mini-Rev. Med. Chem. , 2007 , 7 : 203 —211
[15 ] 　Kostova I. Curr. Med. Chem. , 2006 , 13 : 1085 —1107
[16 ] 　Hartinger C G, Zorbas-Seifried S , Jakupec M A , et al . J . Inorg.Biochem. , 2006 , 100 : 891 —904
[17 ] 　Jakupec M A , Galanski M, Arion V B , et al . Dalton Trans. , 2008 ,183 —194
[18 ] 　Casini A , Cinellu MA , Minghetti G, et al . J . Med. Chem. , 2006 ,49 : 5524 —5531
[19 ] 　Suresh D , Balakrishna M S , Rathinasamy K, et al . Dalton Trans. ,2008 , 2812 —2814
[20 ] 　Huang R , Wallqvist A , Covell D G. Biochem. Pharmacol . , 2005 ,69 : 1009 —1039
[21 ] 　Li H , Lai C S , Wu J , et al . J . Inorg. Biochem. , 2007 , 101 :809 —816
[22 ] 　Wang G C , Xiao J , Lu Y N , et al . Appl . Organometal . Chem. ,2005 , 19 : 113 —117
[23 ] 　Wang T, Guo ZJ . Curr. Med. Chem. , 2006 , 13 : 525 —537
[24 ] 　Ott I , Gust R. Arch. Pharm. Chem. Life Sci . , 2007 , 340 : 117 —126
[25 ] 　Afrasiabi Z, Sinn E , Lin W, et al . J . Inorg. Biochem. , 2005 , 99 :1526 —1531
[26 ] 　Matkar S S , Wrischnik L A , Jones P R , et al . Biochem. Biophys.Res. Commun. , 2006 , 343 : 754 —761
[27 ] 　Wang D , Lippard SJ . Nature Rev. Drug Dis. , 2005 , 4 : 307 —320
[28 ] 　Jung Y, Lippard S J . Chem. Rev. , 2007 , 107 : 1387 —1407
[29 ] 　Coluccia M, Natile G. Anti-Cancer Agents Med. Chem. , 2007 , 7 :111 —123
[30 ] 　Coley H M, Sarju J , Wagner G. J . Med. Chem. , 2008 , 51 : 135 —141
[31 ] 　Zhang J Y, Wang X Y, Tu C , et al . J . Med. Chem. , 2003 , 46 :3502 —3507
[32 ] 　Gao X L , Wang X Y, Ding J , et al . Inorg. Chem. Commun. ,2006 , 9 : 722 —726
[33 ] 　Wang X Y, Lin J , Zhang X M, et al . J . Inorg. Biochem. , 2003 ,94 : 186 —192
[34 ] 　Martins E T, Baruah H , Kramarczyk J , et al . J . Med. Chem. ,2001 , 44 : 4492 —4496
[35 ] 　Brow J M, Pleatman C R , Bierbach U. Bioorg. Med. Chem. Lett . ,2002 , 12 : 2953 —2955
[36 ] 　Baruah H , Rector CL , Monnier SM, et al . Biochem. Pharmacol . ,2002 , 64 : 191 —200
[37 ] 　Lovejoy K S , Todd R C , Zhang S , et al . Proc. Natl . Acad. Sci .USA , 2008 , 105 : 8902 —8907
[38 ] 　Zhao Y M, He WJ , Shi P F , et al . Dalton Trans. , 2006 , 2617 —2619
[39 ] 　Fan D M, Yang X L , Wang X Y, et al . J . Biol . Inorg. Chem. ,2007 , 12 : 655 —665
[40 ] 　Komeda S , Moulaei T, Woods K K, et al . J . Am. Chem. Soc. ,2006 , 128 : 16092 —16103
[41 ] 　Harris A L , Yang X, Hegmans A , et al . Inorg. Chem. , 2005 , 44 :9598 —9600
[42 ] 　Van Zutphen S , Reedijk J . Coord. Chem. Rev. , 2005 , 249 :2845 —2853
[43 ] 　Yang Z, Wang X Y, Diao H J , et al . Chem. Commun. , 2007 ,3453 —3455
[44 ] 　MacDiarmid J A , Mugridge N B , Weiss J C , et al . Cancer Cell ,2007 , 11 : 431 —445
[45 ] 　Hall MD , Mellor H R , Callaghan R , et al . J . Med. Chem. , 2007 ,50 : 3403 —3411
[46 ] 　Ang W H , Khalaila I , Allardyce C S , et al . J . Am. Chem. Soc. ,2005 , 127 : 1382 —1383
[47 ] 　Feazell R P , Nakayama-Ratchford N , Dai H , et al . J . Am. Chem.Soc. , 2007 , 129 : 8438 —8439
[48 ] 　Ronconi L , Sadler P J . Coord. Chem. Rev. , 2007 , 251 : 1633 —1648
[49 ] 　Bednarski P J , Grünert R , Zielzki M, et al . Chem. Biol . , 2006 ,13 : 61 —67
[50 ] 　Mackay F S , Woods J A , Moseley H , et al . Chem. Eur. J . , 2006 ,12 : 3155 —3161
[51 ] 　Mackay F S , Woods J A , HeringováP , et al . Proc. Natl . Acad.Sci . USA , 2007 , 104 : 20743 —20748
[52 ] 　Mao J F , Zhang Y M, Zhu J H , et al . Chem. Commun. , 2009 ,908 —910
[53 ] 　Heringova P , Woods J , Mackay F S , et al . J . Med. Chem. , 2006 ,49 : 7792 —7798
[54 ] 　Hannon MJ . Pure Appl . Chem. , 2007 , 79 : 2243 —2261
[55 ] 　Ang W H , Dyson P J . Eur. J . Inorg. Chem. , 2006 , 4003 —4018
[56 ] 　Dyson P J , Sava G. Dalton Trans. , 2006 , 1929 —1933
[57 ] 　Bergamo A , Sava G. Dalton Trans. , 2007 , 1267 —1272
[58 ] 　Scolaro C , Bergamo A , Brescacin L , et al . J . Med. Chem. , 2005 ,48 : 4161 —4171
[59 ] 　Habtemariam A , Melchart M, Fernández R , et al . J . Med. Chem. ,2006 , 49 : 6858 —6868
[60 ] 　Yan Y K, Melchart M, Habtemariam A , et al . Chem. Commun. ,2005 , 4764 —4776
[61 ] 　Liu H K, Berners-Price S J , Wang F Y, et al . Angew. Chem. Int .Ed. , 2006 , 45 : 8153 —8156
[62 ] 　Peacock A F A , Parsons S , Sadler PJ . J . Am. Chem. Soc. , 2007 ,129 : 3348 —3357
[63 ] 　Friebolin W, Schilling G, Zê ller M, et al . J . Med. Chem. , 2005 ,48 : 7925 —7931
[64 ] 　Sun R W Y, Ma D L , Wong E L M, et al . Dalton Trans. , 2007 ,4884 —4892
[65 ] 　Wang X Y, Guo ZJ . Dalton Trans. , 2008 , 1521 —1532
[66 ] 　Shi P F , Jiang Q , Zhao Y M, et al . J . Biol . Inorg. Chem. , 2006 ,11 : 745 —752
[67 ] 　Yang T, Tu C , Zhang J Y, et al . Dalton Trans. , 2003 , 3419 —3424
[68 ] 　Shi P F , Jiang Q , Lin J , et al . J . Inorg. Biochem. , 2006 , 100 :939 —945
[69 ] 　Wang X Y, Zhang X M, Lin J , et al . Dalton Trans. , 2003 , 2379 —2380
[70 ] 　Zhang S C , Tu C , Wang X Y, et al . Eur. J . Inorg. Chem. , 2004 ,4028 —4035
[71 ] 　Chen Z F , Wang X Y, Zhu Y G, et al . J . Inorg. Biochem. , 2007 ,101 : 1894 —1902
[72 ] 　Schatzschneider U , Metzler-Nolte N. Angew. Chem. Int . Ed. ,2006 , 45 : 1504 —1507
[73 ] 　Hillard E , Vessières A , Thouin L , et al . Angew. Chem. Int . Ed. ,2006 , 45 : 285 —290
[74 ] 　James P , Neudêrfl J , Eissmann M, et al . Org. Lett . , 2006 , 8 :2763 —2766
[75 ] 　Strohfeldt K, Tacke M. Chem. Soc. Rev. , 2008 , 37 : 1174 —1187
[76 ] 　Koch B , Baul T S B , Chatterjee A. J . Appl . Toxicol . , 2008 , 28 :430 —438
[77 ] 　Meggers E , Atilla-Gokcumen G E , Bregman H , et al . Synlett ,2007 , 1177 —1189
[78 ] 　Bregman H , Carroll P J , Meggers E. J . Am. Chem. Soc. , 2006 ,128 : 877 —884
[79 ] 　Smalley K S M, Contractor R , Haass N K, et al . Cancer Res. ,2007 , 67 : 209 —217
[80 ] 　Reed J E , Arnal A A , Neidle S , et al . J . Am. Chem. Soc. , 2006 ,128 : 5992 —5993
[81 ] 　Dixon I M, Lopez F , Tejera A M, et al . J . Am. Chem. Soc. ,2007 , 129 : 1502 —1503
[82 ] 　Kieltyka R , Fakhoury J , Moitessier N , et al . Chem. Eur. J . ,2008 , 14 : 1145 —1154
[83 ] 　Kieltyka R , Englebienne P , Fakhoury J , et al . J . Am. Chem.Soc. , 2008 , 130 : 10040 —10041
[84 ] 　Pennington J D , Jacobs KM, Sun L , et al . Curr. Pharm. Design ,2007 , 13 : 3368 —3377
[85 ] 　Urig S , Fritz-Wolf K, Réau R , et al . Angew. Chem. Int . Ed. ,2006 , 45 : 1881 —1886
[86 ] 　Barnard P J , Berners-Price S J . Coord. Chem. Rev. , 2007 , 251 :1889 —1902
[87 ] 　Wang Y, He Q Y, Che CM, et al . Proteomics , 2006 , 6 : 131 —142
[88 ] 　Ott I , Schmidt K, Kircher B , et al . J . Med. Chem. , 2005 , 48 :622 —629
[89 ] 　Failes TW, Cullinane C , Diakos C I , et al . Chem. Eur. J . , 2007 ,13 : 2974 —2982
[90 ] 　Timerbaev A R , Hartinger C G, Aleksenko S S , et al . Chem.Rev. , 2006 , 106 : 2224 —2248
[91 ] 　Calderone V , Casini A , Mangani S , et al . Angew. Chem. Int .Ed. , 2006 , 45 : 1267 —1269
[92 ] 　Casini A , Mastrobuoni G, Ang W H , et al . Chem. Med. Chem. ,2007 , 2 : 631 —635
[93 ] 　Weidt S K, Mackay C L , Langridge-Smith P R R , et al . Chem.Commun. , 2007 , 1719 —1721
[94 ] 　Hartinger C G, Tsybin YO , Fuchser J , et al . Inorg. Chem. , 2008 ,47 : 17 —19
[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] 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.
[3] 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.
[4] 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.
[5] 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.
[6] 赖欣宜, 王志勇, 郑永太, 陈永明. 纳米金属有机框架材料在药物递送领域的应用[J]. 化学进展, 2019, 31(6): 783-790.
[7] 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.
[8] 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.
[9] 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.
[10] 沈娟, 朱阳, 师红东, 刘扬中. 铂类抗癌药物的多功能纳米递送体系[J]. 化学进展, 2018, 30(10): 1557-1572.
[11] 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.
[12] 蒋革, 罗锋, 徐耀忠, 张晓辉. 近紫外光辅助4-硫脱氧胸苷抗癌作用的研究[J]. 化学进展, 2016, 28(8): 1224-1237.
[13] 邓云盼, 杨波, 余刚, 卓琼芳, 邓述波, 张鸿. 金属配合物催化氢解脱卤研究[J]. 化学进展, 2016, 28(4): 564-576.
[14] 陈峰, 白赢, 厉嘉云, 肖文军, 彭家建. 氮配位过渡金属配合物在硅氢加成反应中的应用研究[J]. 化学进展, 2015, 27(7): 806-817.
[15] 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.