Citation: Li Zhiying, Ding Yanjiao, Bu Huagang, Shen Yuemao. Antitumor and DNA Topoisomerase Ⅱα Inhibitory Activity of 6-Substituted-aryl-2-methoxyquinolines[J]. Chinese Journal of Organic Chemistry, ;2018, 38(12): 3204-3210. doi: 10.6023/cjoc201806015 shu

Antitumor and DNA Topoisomerase Ⅱα Inhibitory Activity of 6-Substituted-aryl-2-methoxyquinolines

a.
Key Laboratory of Chemical Biology(Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012
b.
Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021

Corresponding author: Shen Yuemao, yshen@sdu.edu.cn
Received Date: 12 June 2018
Revised Date: 5 August 2018
Available Online: 5 December 2018
Fund Project: Project supported by the National Basic Research Program of China (973 Program, No. 2010CB833802), the National Natural Science Foundation of China (Nos. 81373304, 81502921, 90913024) and the Distinguished Young Scholars Grant (No. 30325044)

Figures(4)

Human DNA Topoisomerase Ⅱα (Topo Ⅱα) is one of the important therapeutic targets for the treatment of cancers. Our previous study showed that p-terphenyls have inhibitory effects on Topo Ⅱα and inhibit the proliferation of human breast ductal carcinoma cells. In this study, nineteen 6-substituted aryl-2-methoxyquinolines (3a~3s) were designed, synthesized and evaluated for their cytotoxicity against the growth of human triple negative breast cancer MDA-MB-231 cell line and inhibitory activity against Topo Ⅱα. Among these compounds, 6-(4-(hydroxymethyl)phenyl)-2-methoxyquinoline (3b) showed the most potent activity (IC₅₀=9.9 μmol·L^-1). These results have important significance for the further study of aryl quinoline TopoⅡα inhibitors.
- Topoisomerase Ⅱα,
- Synthesis,
- Structure optimization,
- Antitumor activity
1. [1]
  Wang, J. C. Annu. Rev. Biochem. 1996, 65, 635. doi: 10.1146/annurev.bi.65.070196.003223
2. [2]
  Azarova, A. M.; Lyu, Y. L.; Lin, C. P.; Tsai, Y. C.; Lau, J. Y.; Wang, J. C.; Liu, L. F. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 11014. doi: 10.1073/pnas.0704002104
3. [3]
  Deweese, J. E.; Osheroff, N. Nucleic Acids Res. 2009, 37, 738. doi: 10.1093/nar/gkn937
4. [4]
  Haffner, M. C.; Aryee, M. J.; Toubaji, A.; Esopi, D. M.; Albadine, R.; Gurel, B.; Isaacs, W. B.; Bova, G. S.; Liu, W.; Xu, J.; Meeker, A. K.; Netto, G.; De Marzo, A. M.; Nelson, W. G.; Yegnasubramanian, S. Nat. Genetics 2010, 42, 668. doi: 10.1038/ng.613
5. [5]
  Liu, S. S.; Zhao, B. B.; Lu, C. H.; Huang, J. J.; Shen, Y. M. Nat. Prod. Commun. 2012, 7, 1057.
6. [6]
  Qiu, J.; Zhao, B.; Shen, Y.; Chen, W.; Ma, Y.; Shen, Y. Eur. J. Med. Chem. 2013, 68, 192. doi: 10.1016/j.ejmech.2013.07.020
7. [7]
  Ibrahim, M. K.; Taghour, M. S.; Metwaly, A. M.; Belal, A.; Mehany, A. B. M.; Elhendawy, M. A.; Yassin, M. M.; Yassin, A. M.; El-Deeb, N. M.; Hafez, E. E.; Elsohly, M. A.; Eissa, I. H. Eur. J. Med. Chem. 2018, 115, 117.
8. [8]
  Kaur, G.; Cholia, R. P.; Joshi, G.; Amrutkar, S. M.; Kalra, S.; Mantha, A. K.; Banerjee, U. C.; Kumar, R.. Pham. Chem. Life Sci. 2018, 351, e1800023. doi: 10.1002/ardp.v351.6
9. [9]
  Ruchelman, A. L.; Singh, S. K.; Wu, X.; Ray, A.; Yang, J. M.; Li, T. K.; Liu, A.; Liu, L. F.; LaVoie, E. J. Bioorg. Med. Chem. Lett. 2002, 12, 3333. doi: 10.1016/S0960-894X(02)00737-0
10. [10]
  Lu, C. M.; Chen, Y. L.; Chen, H. L; Chen, C. A.; Lu, P. J.; Yang, C. N.; Tzeng, C. C. Bioorg. Med. Chem. 2010, 18, 1948.
11. [11]
  Carmichael, J.; DeGraff, W. G.; Gazdar, A. F.; Minna, J. D.; Mitchell, J. B. Cancer Res 1987, 47, 936.
12. [12]
  Huang, Y.; Wang, J.; Li, G.; Zheng, Z.; Su, W. FEMS Immunol. Med. Microbiol. 2001, 31, 163. doi: 10.1111/fim.2001.31.issue-2
13. [13]
  Chen, W.; Shen, Y.; Li, Z.; Zhang, M.; Lu, C.; Shen, Y. Eur. J. Med. Chem. 2014, 86, 782. doi: 10.1016/j.ejmech.2014.08.073
14. [14]
  Shen, Y.; Chen, W.; Zhao, B.; Hao, H.; Li, Z.; Lu, C.; Shen, Y. Biochem. Biophys. Res. Commun. 2014, 453, 302. doi: 10.1016/j.bbrc.2014.09.042
15. [15]
  Shen, Y.; Chen, W.; Li, Z.; Shen, Y. Med. Chem. 2014, 10, 533. doi: 10.2174/15734064113096660048
16. [16]
  Barrett, J.; Sutcliffe, J.; Gootz, T. Antimicrob. Agents Chemother. 1990, 34, 1. doi: 10.1128/AAC.34.1.1
17. [17]
  Marini, J. C.; Levene, S. D.; Crothers, D. M.; Englund, P. T. Proc. Natl. Acad. Sci. 1982, 79, 7664. doi: 10.1073/pnas.79.24.7664
18. [18]
  Xiao, X.; Cushman, M. J. Am. Chem. Soc. 2005, 127, 9960. doi: 10.1021/ja042485n
19. [19]
  Trott, O.; Olson, A. J. J. Comput. Chem. 2010, 31, 455.
20. [20]
  Sanner, M. F. J. Mol.-Graphies Modell. 1999, 17, 57.
21. [21]
  Morris, G. M.; Huey, R.; Lindstrom, W.; Sanner, M. F.; Belew, R. K.; Goodsell, D. S.; Olson, A. J. J. Comput. Chem. 2009, 30, 2785. doi: 10.1002/jcc.v30:16
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