Citation: Bin Li, Chun-Mei Gao, Qin-Sheng Sun, Lu-Lu Li, Chun-Yan Tan, Hong-Xia Liu, Yu-Yang Jiang. Novel synthetic acridine-based derivatives as topoisomerase I inhibitors[J]. Chinese Chemical Letters, ;2014, 25(7): 1021-1024. doi: 10.1016/j.cclet.2014.03.028 shu

Novel synthetic acridine-based derivatives as topoisomerase I inhibitors

Bin Li ^a,b ,
Chun-Mei Gao ^b,c,, ,
Qin-Sheng Sun ^b ,
Lu-Lu Li ^b ,
Chun-Yan Tan ^b,c ,
Hong-Xia Liu ^b ,
Yu-Yang Jiang ^b,c,d,,

1.
a Tsinghua University, Department of Chemistry, Beijing 100084, China;
2.
b The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, Shenzhen 518055, China;
3.
c Shenzhen Anti-Tumor Drug Development Engineering Laboratory, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China;
4.
d School of Medicine, Tsinghua University, Beijing 100084, China

Corresponding author: Chun-Mei Gao, Yu-Yang Jiang,
Received Date: 25 December 2013
Available Online: 5 March 2014
Fund Project:

Novel DNA binding agents against topoisomerases are needed for effective treatment of cancers. A series of new acridine-based derivatives 7a-7d were synthesized and their antiproliferative activity against K562 and HepG-2 cell lines were evaluated. Compound 7c with pyridin-2-yl-methanamino group substituted at the C9 position of acridine showed good antitumor activity against both cell lines. The DNA-binding affinity of compound 7c was evaluated by UV-vis absorption spectra and fluorescence emission spectra. DNA topoisomerase I mediated relaxation of plasmid pBR322 DNA was also tested. Our results suggested that compound 7c with good antitumor activity and topoisomerase I inhibition activity can be developed as a prime candidate for further chemical optimization.
- Acridine,
- DNA binding agent,
- Topoisomerase,
- Anticancer
1. [1]
  [1] I. Kümler, N. Brünner, J. Stenvang, E. Balslev, D.L. Nielsen, A systematic review on topoisomerase I inhibition in the treatment of metastatic breast cancer, Breast Cancer Res. Treat. 138 (2013) 347-358.
2. [2]
  [2] X. Zhang, B. Bao, X.H. Yu, et al., The discovery and optimization of novel dual inhibitors of topoisomerase II and histone deacetylase, Bioorg. Med. Chem. 21 (2013) 6981-6995.
3. [3]
  [3] S.M.B. Nijman, S.H. Friend, Cancer. Potential of the synthetic lethality principle, Science 342 (2013) 809-811.
4. [4]
  [4] Y. Li, H.B. Zhang, W.L. Huang, X. Zhen, Y.M. Li, Synthesis and biological evaluation of tetrahydroisoquinoline derivatives as potential multidrug resistance reversal agents in cancer, Chin. Chem. Lett. 19 (2008) 169-171.
5. [5]
  [5] L.H. Shen, Y. Li, D.H. Zhang, Y.S. Lai, L.J. Liu, Synthesis and evaluation of nitrate derivatives of colchicine as anticancer agents, Chin. Chem. Lett. 22 (2011) 768-770.
6. [6]
  [6] C. Kaplan-Ozen, B. Tekiner-Gulbas, E. Foto, et al., Benzothiazole derivatives as human DNA topoisomerase II alpha inhibitors, Med. Chem. Res. 22 (2013) 5798-5808.
7. [7]
  [7] Z.Y. Tian, H.X. Ma, S.Q. Xie, et al., Synthesis, DNA binding and topoisomerase inhibition of mononaphthalimide homospermidine derivatives, Chin. Chem. Lett. 19 (2008) 509-512.
8. [8]
  [8] J.R. Goodell, A.V. Ougolkov, H. Hiasa, et al., Acridine-based agents with topoisomerase II activity inhibit pancreatic cancer cell proliferation and induce apoptosis, J. Med. Chem. 51 (2012) 179-182.
9. [9]
  [9] K. Padget, A. Stewart, P. Charlton, M.J. Tilby, C.A. Austin, An investigation into the formation of N-2-(dimethylamino)ethyl acridine-4-carboxamide (DACA) and 6-2-(dimethylamino)ethylamino-3-hydroxy-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103) stabilised DNA topoisomerase I and II cleavable complexes in human leukaemia cells, Biochem. Pharmacol. 60 (2000) 817-821.
10. [10]
  [10] J.Y. Chang, C.F. Lin, W.Y. Pan, et al., New analogues of AHMA as potential antitumor agents: synthesis and biological activity, Bioorg. Med. Chem. 11 (2003) 4959-4969.
11. [11]
  [11] K. Rastogi, J.Y. Chang, W.Y. Pan, et al., Antitumor AHMA linked to DNA minor groove binding agents: synthesis and biological evaluation, J. Med. Chem. 45 (2002) 4485-4493.
12. [12]
  [12] R. Zittoun, m-AMSA: a review of clinical data, Eur. J. Cancer Clin. Oncol. 21 (1985) 649-653.
13. [13]
  [13] T.L. Su, T.C. Chou, J.Y. Kim, et al., 9-Substituted acridine-derivatives with long halflife and potent antitumor-activity-synthesis and structure-activity-relationships, J. Med. Chem. 38 (1995) 3226-3235.
14. [14]
  [14] I. Gonzalez-Sanchez, J.D. Solano, M.A. Loza-Mejia, et al., Antineoplastic activity of the thiazolo 5, 4-b quinoline derivative D3CLP in K-562 cells is mediated through effector caspases activation, Eur. J. Med. Chem. 46 (2011) 2102-2108.
15. [15]
  [15] C.H. Chen, Y.W. Lin, X.G. Zhang, et al., Synthesis and in vitro cytotoxicity of 9-anilinoacridines bearing N-mustard residue on both anilino and acridine rings, Eur. J. Med. Chem. 44 (2009) 3056-3059.
16. [16]
  [16] X.D. Luan, C.M. Gao, N.N. Zhang, et al., Exploration of acridine scaffold as a potentially interesting scaffold for discovering novel multi-target VEGFR-2 and Src kinase inhibitors, Bioorg. Med. Chem. 19 (2011) 3312-3319.
17. [17]
  [17] Y.Q. Li, C.Y. Tan, C.M. Gao, et al., Discovery of benzimidazole derivatives as novel multi-target EGFR, VEGFR-2 and PDGFR kinase inhibitors, Bioorg. Med. Chem. 19 (2011) 4529-4535.
18. [18]
  [18] X.L. Lang, L.L. Li, Y.Z. Chen, et al., Novel synthetic acridine derivatives as potent DNA-binding and apoptosis-inducing antitumor agents, Bioorg. Med. Chem. 21 (2013) 4170-4177.
19. [19]
  [19] X.L. Lang, Q.S. Sun, Y.Z. Chen, et al., Novel synthetic 9-benzyloxyacridine analogue as both tyrosine kinase and topoisomerase I inhibitor, Chin. Chem. Lett. 24 (2013) 677-680.
20. [20]
  [20] C.M. Gao, F. Liu, X.D. Luan, et al., Novel synthetic 2-amino-10-(3, 5-dimethoxy) benzyl-9(10H)-acridinone derivatives as potent DNA-binding antiproliferative agents, Bioorg. Med. Chem. 18 (2010) 7507-7514.
21. [21]
  [21] C.M. Gao, S.F. Li, X.L. Lang, et al., Synthesis and evaluation of 10-(3, 5-dimethoxy) benzyl-9(10H)-acridone derivatives as selective telomeric G-quadruplex DNA ligands, Tetrahedron 68 (2012) 7920-7925.
22. [22]
  [22] X.D. Luan, C.M. Gao, Q.S. Sun, et al., Novel synthetic azaacridine analogues as topoisomerase 1 inhibitors, Chem. Lett. 40 (2011) 728-729.
23. [23]
  [23] X.L. Lang, X.D. Luan, C.M. Gao, Y.Y. Jiang, Recent progress of acridine derivatives with antitumor activity, Prog. Chem. 24 (2012) 1497-1505.
1. [1]
  Yao HUANG , Yingshu WU , Zhichun BAO , Yue HUANG , Shangfeng TANG , Ruixue LIU , Yancheng LIU , Hong LIANG . Copper complexes of anthrahydrazone bearing pyridyl side chain: Synthesis, crystal structure, anticancer activity, and DNA binding. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 213-224. doi: 10.11862/CJIC.20240359
2. [2]
  Xiaofen GUAN , Yating LIU , Jia LI , Yiwen HU , Haiyuan DING , Yuanjing SHI , Zhiqiang WANG , Wenmin WANG . Synthesis, crystal structure, and DNA-binding of binuclear lanthanide complexes based on a multidentate Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2486-2496. doi: 10.11862/CJIC.20240122
3. [3]
  Wenkai Liu , Yanxian Hou , Weijian Liu , Ran Wang , Shan He , Xiang Xia , Chengyuan Lv , Hua Gu , Qichao Yao , Qingze Pan , Zehou Su , Danhong Zhou , Wen Sun , Jiangli Fan , Xiaojun Peng . Se-substituted pentamethine cyanine for anticancer photodynamic therapy mediated using the hot band absorption process. Chinese Chemical Letters, 2024, 35(12): 109631-. doi: 10.1016/j.cclet.2024.109631
4. [4]
  Tong Tong , Lezong Chen , Siying Wu , Zhong Cao , Yuanbin Song , Jun Wu . Establishment of a leucine-based poly(ester amide)s library with self-anticancer effect as nano-drug carrier for colorectal cancer treatment. Chinese Chemical Letters, 2024, 35(12): 109689-. doi: 10.1016/j.cclet.2024.109689
5. [5]
  Shangqian Zhang , Jiaxuan Li , Xuan Hu , Zelong Chen , Junliang Dong , Chenhao Hu , Shuang Chao , Yinghua Lv , Yuxin Pei , Zhichao Pei . H₂S and NIR light-driven nanomotors induce disulfidptosis for targeted anticancer therapy by enhancing disruption of tumor metabolic symbiosis. Chinese Chemical Letters, 2025, 36(1): 110314-. doi: 10.1016/j.cclet.2024.110314
6. [6]
  Tao LIU , Yuting TIAN , Ke GAO , Xuwei HAN , Ru'nan MIN , Wenjing ZHAO , Xueyi SUN , Caixia YIN . A photothermal agent with high photothermal conversion efficiency and high stability for tumor therapy. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1622-1632. doi: 10.11862/CJIC.20240107
7. [7]
  Chang Liu , Tao Wu , Lijiao Deng , Xuzi Li , Xin Fu , Shuzhen Liao , Wenjie Ma , Guoqiang Zou , Hai Yang . Programmed DNA walkers for biosensors. Chinese Chemical Letters, 2024, 35(9): 109307-. doi: 10.1016/j.cclet.2023.109307
8. [8]
  Jia-Li Xie , Tian-Jin Xie , Yu-Jie Luo , Kai Mao , Cheng-Zhi Huang , Yuan-Fang Li , Shu-Jun Zhen . Octopus-like DNA nanostructure coupled with graphene oxide enhanced fluorescence anisotropy for hepatitis B virus DNA detection. Chinese Chemical Letters, 2024, 35(6): 109137-. doi: 10.1016/j.cclet.2023.109137
9. [9]
  Wu-Jian Long , Yang Yu , Chuang He . A novel and promising engineering application of carbon dots: Enhancing the chloride binding performance of cement. Chinese Chemical Letters, 2024, 35(6): 108943-. doi: 10.1016/j.cclet.2023.108943
10. [10]
  Yulin Mao , Jingyu Ma , Jiecheng Ji , Yuliang Wang , Wanhua Wu , Cheng Yang . Crown aldoxime ethers: Their synthesis, structure, acid-catalyzed/photo-induced isomerization and adjustable guest binding. Chinese Chemical Letters, 2024, 35(11): 109927-. doi: 10.1016/j.cclet.2024.109927
11. [11]
  Lihua Gao , Yinglei Han , Chensheng Lin , Huikang Jiang , Guang Peng , Guangsai Yang , Jindong Chen , Ning Ye . Halogen-assisted octet binding electrons construction of pnictogens towards wide-bandgap nonlinear optical pnictides. Chinese Chemical Letters, 2024, 35(12): 109529-. doi: 10.1016/j.cclet.2024.109529
12. [12]
  Xixian Sun , Shengke Li , Ruibing Wang , Leyong Wang . Functional macrocyclic arenes with active binding sites inside cavity for biomimetic molecular recognition. Chinese Chemical Letters, 2025, 36(4): 110806-. doi: 10.1016/j.cclet.2024.110806
13. [13]
  Yang Qin , Jiangtian Li , Xuehao Zhang , Kaixuan Wan , Heao Zhang , Feiyang Huang , Limei Wang , Hongxun Wang , Longjie Li , Xianjin Xiao . Toeless and reversible DNA strand displacement based on Hoogsteen-bond triplex. Chinese Chemical Letters, 2024, 35(5): 108826-. doi: 10.1016/j.cclet.2023.108826
14. [14]
  Xiaohong Wen , Mei Yang , Lie Li , Mingmin Huang , Wei Cui , Suping Li , Haiyan Chen , Chen Li , Qiuping Guo . Enzymatically controlled DNA tetrahedron nanoprobes for specific imaging of ATP in tumor. Chinese Chemical Letters, 2024, 35(8): 109291-. doi: 10.1016/j.cclet.2023.109291
15. [15]
  Jingwen Zhao , Jianpu Tang , Zhen Cui , Limin Liu , Dayong Yang , Chi Yao . A DNA micro-complex containing polyaptamer for exosome separation and wound healing. Chinese Chemical Letters, 2024, 35(9): 109303-. doi: 10.1016/j.cclet.2023.109303
16. [16]
  Zhongyu Wang , Lijun Wang , Huaixin Zhao . DNA-based nanosystems to generate reactive oxygen species for nanomedicine. Chinese Chemical Letters, 2024, 35(11): 109637-. doi: 10.1016/j.cclet.2024.109637
17. [17]
  Jiangshan Xu , Weifei Zhang , Zhengwen Cai , Yong Li , Long Bai , Shaojingya Gao , Qiang Sun , Yunfeng Lin . Tetrahedron DNA nanostructure/iron-based nanomaterials for combined tumor therapy. Chinese Chemical Letters, 2024, 35(11): 109620-. doi: 10.1016/j.cclet.2024.109620
18. [18]
  Xiaoyao Ma , Jinling Zhang , Ge Fang , He Gao , Jie Gao , Li Fu , Yuanyuan Hou , Gang Bai . Förster resonance energy transfer reveals phillygenin and swertiamarin concurrently target AKT on different binding domains to increase the anti-inflammatory effect. Chinese Chemical Letters, 2024, 35(5): 108823-. doi: 10.1016/j.cclet.2023.108823
19. [19]
  Tian Feng , Yun-Ling Gao , Di Hu , Ke-Yu Yuan , Shu-Yi Gu , Yao-Hua Gu , Si-Yu Yu , Jun Xiong , Yu-Qi Feng , Jie Wang , Bi-Feng Yuan . Chronic sleep deprivation induces alterations in DNA and RNA modifications by liquid chromatography-mass spectrometry analysis. Chinese Chemical Letters, 2024, 35(8): 109259-. doi: 10.1016/j.cclet.2023.109259
20. [20]
  Zhe-Han Yang , Jie Yin , Lei Xin , Yuanfang Li , Yijie Huang , Ruo Yuan , Ying Zhuo . Research advancement of DNA-based intelligent hydrogels: Manufacture, characteristics, application of disease diagnosis and treatment. Chinese Chemical Letters, 2024, 35(10): 109558-. doi: 10.1016/j.cclet.2024.109558

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(604)
HTML views(1)

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