Citation: Fan Rong, Yang Zhibin, Bian Mianli, Liu Wukun. Progress in Antitumor Activity of Metal N-Heterocyclic Carbene Complexes[J]. Chemistry, ;2020, 83(4): 308-317. shu

Progress in Antitumor Activity of Metal N-Heterocyclic Carbene Complexes

Fan Rong ¹ ,
Yang Zhibin ^1,2 ,
Bian Mianli ¹ ,
Liu Wukun ^1,3,,

1.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023
2.
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali, 671000
3.
State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing, 210023

Corresponding author: Liu Wukun, liuwukun0000@njucm.edu.cn
Received Date: 18 November 2019
Accepted Date: 12 January 2020

Figures(5)

Since the successful development of cisplatin as a clinical anticancer drug in 1978, the development of metal complexes as small molecule anticancer drugs has become a research hotspot. Because of the formation of stable covalent bonds between N-heterocyclic carbene and various transition metal centers, metal N-heterocyclic carbene complexes have the potential to be developed into drugs. Recently, metal N-heterocyclic carbene complexes have been found to have good anticancer activities, which have stimulated the research enthusiasm of the majority of inorganic medicinal chemistry researchers. Based on our previous study of metal N-heterocyclic carbene complexes as antitumor agents, in this review, the antitumor activities and mechanisms of silver, gold, rhodium and platinum N-heterocyclic carbene complexes are summarized. We hope this review could provide a reference for the design and synthesis of metal N-heterocyclic carbene complexes as antitumor agents.
- Cisplatin,
- Metal N-heterocyclic carbene complexes,
- Mechanism,
- Antitumor
1. [1]
2. [2]
  Jung Y, Lippard S J. Chem. Rev., 2007, 107(5):1387~1407.
3. [3]
4. [4]
  Hindi K M, Panzner M J, Tessier C A, et al. Chem. Rev., 2009, 109(8):3859~3884.
5. [5]
  Wang Y T, Gao B B, Wang F, et al. Dalton. Transac., 2017, 46(6):1832~1839.
6. [6]
  Bao S J, Liu C Y, Zhang M, et al. Coord. Chem. Rev., 2019, 397:28~53.
7. [7]
  Huynh H V. Chem. Rev., 2018, 118(19):9457~9492.
8. [8]
  Melaiye A, Simons R S, Milsted A, et al. J. Med. Chem., 2004, 47(4):973~977.
9. [9]
  Medvetz D A, Hindi K M, Panzner M J, et al. Met.-Based Drugs, 2008, 2008:1~7.
10. [10]
  Hackenberg F, Lally G, Müller-Bunz H, et al. J. Organomet. Chem., 2012, 717:123~134.
11. [11]
  Streciwilk W, Cassidy J, Hackenberg F, et al. J. Organomet. Chem., 2014, 749:88~99.
12. [12]
  Hackenberg F, Lally G, Müller-Bunz H, et al. Inorg. Chim. Acta, 2013, 395:135~144.
13. [13]
  Iduna F, Jindrich C, Martin M, et al. Lett. Drug Des. Discov., 2012, 9(9):815~822.
14. [14]
  Liu W, Bensdorf K, Hagenbach A, et al. Eur. J. Med. Chem., 2011, 46(12):5927~5934.
15. [15]
  Eloy L, Jarrousse A S, Teyssot M L, et al. ChemMedChem, 2012, 7(5):805~814.
16. [16]
  Li Y, Liu G F, Tan C P, et al. Metallomics, 2014, 6(8):1460~1468.
17. [17]
  Shruti K, Batakrishna J, Abhijit S, et al. Dalton Transac., 2014, 43(26):9838~9842.
18. [18]
  Citta A, Schuh E, Mohr F, et al. Metallomics, 2013, 5(8):1006~1015.
19. [19]
  Liang X, Luan S, Yin Z, et al. Eur. J. Med. Chem., 2018, 157:62~80.
20. [20]
  Benoît B, Angela C. Dalton Transac., 2014, 43(11):4209~4219.
21. [21]
  Wragg D, de Almeida A, Bonsignore R, et al. Angew. Chem. Int. Ed., 2018, 57(44):14524~14528.
22. [22]
  Porchia M, Pellei M, Marinelli M, et al. Eur. J. Med. Chem., 2018, 146:709~746.
23. [23]
  Madeira J M, Gibson D L, Kean W F, et al. Inflammopharmacology, 2012, 20(6):297~306.
24. [24]
  Warren F, Nakhle S, Min S, et al. Cancer Res., 2014, 74(9):2520~2532.
25. [25]
  Zhang B, Zhang J, Peng S, et al. Expert Opin. Ther. Pat., 2017, 27(5):547~556.
26. [26]
  Karaca O, Meier-Menches S M, Casini A, et al. Chem. Commun., 2017, 53(59):8249~8260.
27. [27]
  Holenya P, Can S, Rubbiani R, et al. Metallomics, 2014, 6(9):1591~1601.
28. [28]
  Bian M, Fan R, Zhao S, et al. J. Med. Chem., 2019, 62(16):7309~7321.
29. [29]
  Rubbiani R, Kitanovic I, Alborzinia H, et al. J. Med. Chem., 2010, 53(24):8608~8618.
30. [30]
  Zhang J, Zhang B, Li X, et al. Med. Res. Rev., 2017, 27(5):547~556.
31. [31]
  Wedlock L E, Kilburn M R, Cliff J B, et al. Metallomics, 2011, 3(9):917~925.
32. [32]
  Wang H M J, Lin I J B. Organometallics, 1998, 17(5):972~975.
33. [33]
  Hickey J L, Ruhayel R A, Barnard P J, et al. J. Am. Chem. Soc., 2008, 130(38):12570~12571.
34. [34]
  Hickey J L, Ruhayel R A, Barnard P J, et al. J. Am. Chem. Soc., 2008, 130(38):12570~12571.
35. [35]
  Liu W, Bensdorf K, Proetto M, et al. J. Med. Chem., 2011, 54(24):8605~8615.
36. [36]
  Liu W, Bensdorf K, Proetto M, et al. J. Med. Chem., 2012, 55(8):3713~3724.
37. [37]
  Rubbiani R, Can S, Kitanovic I, et al. J. Med. Chem., 2011, 54(24):8646~8657.
38. [38]
  Meyer A, Oehninger L, Geldmacher Y, et al. ChemMedChem, 2014, 9(8):1794~1800.
39. [39]
  Pratesi A, Gabbiani C, Michelucci E, et al. J. Inorg. Biochem., 2014, 136(7):161~169.
40. [40]
  Lum C T, Sun R W, Zou T, et al. Chem. Sci., 2014, 5(4):1579~1584.
41. [41]
  Fung S K, Zou T, Cao B, et al. Angew. Chem. Int. Ed., 2017, 56(14):3892~3896.
42. [42]
  McConnell J R, Rananaware D P, Ramsey D M, et al. Bioorg. Med. Chem. Lett., 2013, 23(9):2527~2531.
43. [43]
  Oehninger L, Küster L N, Schmidt C, et al. Chem. Eur. J., 2013, 19(52):17871~17880.
44. [44]
  Oehninger L, Spreckelmeyer S, Holenya P, et al. J. Med. Chem., 2015, 58(24):9591~9600.
45. [45]
  Streciwilk W, Terenzi A, Cheng X, et al. Eur. J. Med. Chem., 2018, 156:148~161.
46. [46]
  Fan R, Bian M, Hu L, et al. Eur. J. Med. Chem., 2019, 183:111721.
47. [47]
  Skander M, Retailleau P, Bourrié B, et al. J. Med. Chem., 2010, 53(5):2146~2154.
48. [48]
  Chtchigrovsky M, Eloy L, Jullien H, et al. J. Med. Chem., 2013, 56(5):2074~2086.
49. [49]
  Zhang J J, Che C M, Ott I. J. Organomet. Chem., 2015, 782:37~41.
50. [50]
  Li K, Zou T, Chen Y, et al. Chem. Eur. J., 2015, 21(20):7441~7453.
51. [51]
  Betzer J F, Nuter F, Chtchigrovsky M, et al. Bioconjug. Chem., 2016, 27(6):1456~1470.
1. [1]
  Hanxue LIU , Shijie LI , Meng REN , Xuling XUE , Hongke LIU . Design and antitumor properties of dehydroabietic acid functionalized cyclometalated iridium(Ⅲ) complex. Chinese Journal of Inorganic Chemistry, 2025, 41(8): 1483-1494. doi: 10.11862/CJIC.20250031
2. [2]
  Xiaotong LU , Pan ZHANG , Zijie ZHAO , Lei HUANG , Hongwei ZUO , Lili LIANG . Antitumor and antibacterial activities of pyridyl Schiff base indium and dysprosium complexes. Chinese Journal of Inorganic Chemistry, 2025, 41(8): 1523-1532. doi: 10.11862/CJIC.20250073
3. [3]
  Jiahao Zeng , Hui Chao . 诱导程序性细胞死亡的金属抗肿瘤药物研究. University Chemistry, 2025, 40(6): 145-159. doi: 10.12461/PKU.DXHX202406019
4. [4]
  Ping Song , Nan Zhang , Jie Wang , Rui Yan , Zhiqiang Wang , Yingxue Jin . Experimental Teaching Design on Synthesis and Antitumor Activity Study of Cu-Pyropheophorbide-a Methyl Ester. University Chemistry, 2024, 39(6): 278-286. doi: 10.3866/PKU.DXHX202310087
5. [5]
  Fa Wang , Yu Chen , Hui Chao . Ruthenium(II) Complexes as Photoactivated Chemo-Prodrugs for Hypoxic Tumor Therapy. University Chemistry, 2025, 40(7): 200-212. doi: 10.12461/PKU.DXHX202410024
6. [6]
  Tong Zhou , Liyi Xie , Chuyu Liu , Xiyan Zheng , Bao Li . Between Sobriety and Intoxication: The Fascinating Journey of Sauce-Flavored Latte. University Chemistry, 2024, 39(9): 55-58. doi: 10.12461/PKU.DXHX202312048
7. [7]
  Zimo Shen , Tongwei Zhang , Zhiyi Zhu , Zonghao Gong , Qing Feng , Jinyi Yang , Zhen Li , Min Liu , Wei Qi . From Alkaloid to Anticancer Agent: The Transformative Journey of Camptothecin. University Chemistry, 2025, 40(10): 161-165. doi: 10.12461/PKU.DXHX202411027
8. [8]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
9. [9]
  Huilin ZHENG , Tao WANG , Ruilin GAO , Mengke ZHOU , Xinyue LI , Hui WANG , Xiaoxia GU . Antitumor and antibacterial activities of transition metal complexes incorporating pyridyl salicylaldehyde Schiff base. Chinese Journal of Inorganic Chemistry, 2026, 42(5): 897-905. doi: 10.11862/CJIC.20250358
10. [10]
  Chi Li , Jichao Wan , Qiyu Long , Hui Lv , Ying Xiong . N-Heterocyclic Carbene (NHC)-Catalyzed Amidation of Aldehydes with Nitroso Compounds. University Chemistry, 2024, 39(5): 388-395. doi: 10.3866/PKU.DXHX202312016
11. [11]
  Hong RAO , Yang HU , Yicong MA , Chunxin LÜ , Wei ZHONG , Lihua DU . Synthesis and in vitro anticancer activity of phenanthroline-functionalized nitrogen heterocyclic carbene homo- and heterobimetallic silver/gold complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2429-2437. doi: 10.11862/CJIC.20240275
12. [12]
  Zhihui ZONG , Zijie ZHAO , Lei HUANG , Zhicheng PAN , Shan WANG , Lili LIANG , Huaqing LIU , Enli ZHANG . Synthesis, crystal structures, and antitumor activity of two metal complexes of imidazolyl acylhydrazones. Chinese Journal of Inorganic Chemistry, 2026, 42(5): 1048-1062. doi: 10.11862/CJIC.20250330
13. [13]
  Shuangshuang GAI , Jixiang CAI , Moya YANG , Haijuan WU , Shuzhen FENG , Ming JIANG . Endoplasmic reticulum stress and mitochondrial apoptosis in thiosemicarbazone copper(Ⅱ) complex-triggered triple-negative breast cancer cell death. Chinese Journal of Inorganic Chemistry, 2026, 42(5): 1073-1084. doi: 10.11862/CJIC.20250328
14. [14]
  Xiaoxuan Yu , Wukun Liu . Practice of Ideological and Political Education in Medicinal Chemistry for Pharmacy Administration Major: A Case Study on the Discovery of Cisplatin’s Anticancer Function. University Chemistry, 2025, 40(4): 408-414. doi: 10.12461/PKU.DXHX202405200
15. [15]
  Jian Li , Yu Zhang , Rongrong Yan , Kaiyuan Sun , Xiaoqing Liu , Zishang Liang , Yinan Jiao , Hui Bu , Xin Chen , Jinjin Zhao , Jianlin Shi . Highly Efficient, Targeted, and Traceable Perovskite Nanocrystals for Photoelectrocatalytic Oncotherapy. Acta Physico-Chimica Sinica, 2025, 41(5): 100042-0. doi: 10.1016/j.actphy.2024.100042
16. [16]
  Jiaxun Wu , Mingde Li , Li Dang . The R eaction of Metal Selenium Complexes with Olefins as a Tutorial Case Study for Analyzing Molecular Orbital Interaction Modes. University Chemistry, 2025, 40(3): 108-115. doi: 10.12461/PKU.DXHX202405098
17. [17]
  Yuai Duan , Xuanyu Gan , Yao Fu , Yingjie Cao , Hongliang Han , Zhanfang Ma . Application and Innovative Design of Digital Technology in the Preparation Experiment of Cis(Trans)-Diglycine Copper Complexes. University Chemistry, 2026, 41(1): 373-381. doi: 10.12461/PKU.DXHX202504048
18. [18]
  Zhengqi SHEN , Hanxue LIU , Lin HOU , Meng REN , Xiangyu DAI , Yating ZHANG , Zhi SU , Chao GE , Xuling XUE , Hongke LIU . A dual-pathway synergistic inhibition strategy based on ruthenium/iridium metal complexes targeting GPX4 and DHODH: Mechanism of directly activating ferroptosis in leukemia cells. Chinese Journal of Inorganic Chemistry, 2026, 42(2): 271-283. doi: 10.11862/CJIC.20250230
19. [19]
  Yuxin CHEN , Yanni LING , Yuqing YAO , Keyi WANG , Linna LI , Xin ZHANG , Qin WANG , Hongdao LI , Wenmin WANG . Construction, structures, and interaction with DNA of two Sm^Ⅲ₄ complexes. Chinese Journal of Inorganic Chemistry, 2025, 41(6): 1141-1150. doi: 10.11862/CJIC.20240258
20. [20]
  Changqing MIAO , Fengjiao CHEN , Wenyu LI , Shujie WEI , Yuqing YAO , Keyi WANG , Ni WANG , Xiaoyan XIN , Ming FANG . Crystal structures, DNA action, and antibacterial activities of three tetranuclear lanthanide-based complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2455-2465. doi: 10.11862/CJIC.20240192

Get Citation

PDF

XML

Metrics

PDF Downloads(39)
Abstract views(2554)
HTML views(617)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142