Citation: Wang Chaojie, Cao Qinpo, Yang Hui, Song Panpan, Xue Dengqi, Cui Fei, Gu Yifei, Zhang Xiaosong, Tian Yanan, Zhang Qiurong, Liu Hongmin. Synthesis and Antitumor Activity Evaluation of 3,6-Substituted- 1,2,4-triazolo[3,4-a]phthalazine Derivatives[J]. Chinese Journal of Organic Chemistry, ;2016, 36(7): 1626-1635. doi: 10.6023/cjoc201602004 shu

Synthesis and Antitumor Activity Evaluation of 3,6-Substituted- 1,2,4-triazolo[3,4-a]phthalazine Derivatives

Wang Chaojie ^a,b ,
Cao Qinpo ^a,b ,
Yang Hui ^a,b ,
Song Panpan ^a,b ,
Xue Dengqi ^a,b ,
Cui Fei ^a,b ,
Gu Yifei ^a,b ,
Zhang Xiaosong ^a,b ,
Tian Yanan ^a ,
Zhang Qiurong ^a,b,*,, ,
Liu Hongmin ^a,b,*,,

a.
School of Pharmaceutical Sciences, Zhengzhou 450001
b.
Collaborative Innovation Center of New Drug Research and Saftry Evaluation, Zhengzhou 450001

Corresponding author: Zhang Qiurong, zqr406@sina.com Liu Hongmin, liuhm@zzu.edu.cn
Received Date: 1 February 2016
Revised Date: 3 March 2016

Fund Project: the Basic Research Project of Henan Province No.142300410328the National Natural Science Foundation of China No.81430085

Figures(9)

With the aim of obtaining potential antitumor candidates with more efficiency and more economic value. A series of 3,6-substituted-1,2,4-triazolo[3,4-a]phthalazine derivatives were synthesized. The target products were obtained via cyclization, chlorination, substitution, cyclization, substituted with phthalic anhydride used as the starting material. The structures of target products are confirmed by ¹H NMR, ^I3C NMR, HRMS. A series of 3,6-substituted-1,2,4-triazolo[3,4-a] phthalazine derivatives was evaluated for anticancer activity on four human cancer cell lines including EC-9706, HeLa and MCF-7 by MTT assay. Among them, compound 5d was more cytotoxic against EC-9706 and HeLa cell lines, with IC₅₀ values ranging from 3.9 to 4.5 μmol·L^-¹, which are superior or comparable to 5-Fuorouracil. Flow cytometry analysis indicated that compound 5d induced the cellular early apoptosis and cell cycle arrest in G2/M phase in EC-9706.
- Triazole,
- Phthalazine,
- Antitumor,
- Apoptosis,
- Cell cycle arrest
1. [1]
  American Caneer Society. Cancer facts and figures, statisties for 2009. http: //www.caneer.org/docroot.
2. [2]
  Miller-Moslin, K.; Peukert, S.; Jain, R. K.; McEwan, M. A.; Karki, R.; Llamas, L.; Yusuff, N.; He, F.; Li, Y.; Sun, Y.; Dai, M.; Perez, L.; Michae, W.; Sheng, T.; Lei, H.; Zhang, R.; Williams, J.; Bourret, A.; Ramamurthy, A.; Yuan, J.; Guo, R.; Matsumoto, M.; Vattay, A.; Maniara, W.; Amara, A.; Dorsch, M.; Kellehe, J. F. J. Med. Chem. 2009, 52, 3954
3. [3]
  Menear. K, A.; Adcock, C.; Boulter. R.; Cockcroft, X.; Copsey, L.; Cranston, A.; Dillon, K. J.; Drzewieck, J.; Garman, S.; Gomez, S.; Javaid, H.; Kerrigan, F.; Knights, C.; Lau, A.; Loh, V. M.; Matthews, I. T. W.; Moore, S.; O'Conno, M. J.; Smith, G. C. M.; Martin, N. M. B. J. Med. Chem. 2008, 51, 6581.
4. [4]
  Cao, R. H.; Fan, W. X.; Guo, L.; Ma, Q.; Zhang, G. X.; Li, J. R.; Chen, X. M.; Ren, Z. H.; Qiu, L. Q. Eur. J. Med. Chem. 2013, 60, 135.
5. [5]
  Zhao, P. L.; Duan, A. N,; Zou, M.; Yang, H. K.; You, W. W. Bioorg. Med. Chem. Lett. 2012, 22, 4471.
6. [6]
  Stephane, P.; Sook, W. Y.; Martyn, J.; Michael, P. C,; Claire, S. Bioorg. Med. Chem. 2006, 14, 3643.
7. [7]
  Favia, A. D.; Nicolotti, O.; Stefanachi, A.; Leonetti, F.; Carotti, A. Expert Opin. Drug Discovery 2013, 8, 395.
8. [8]
  Swaminathan, R. N.; Stephen, T. H.; Kiyean, N. Bioorg. Med. Chem. Lett. 2006, 16, 5809.
9. [9]
10. [10]
  Sun, X. Y.; Hu, C.; Deng, X. Q.; Wei, C. X.; Sun, Z. G.; Quan, Z. S. Eur. J. Med. Chem. 2010, 45, 4807.
11. [11]
  Katrien, M.; Pal, T.; Kristof, T. J. L.; Gabor, N. Tetrahedron 2007, 63, 3870.
12. [12]
  Street, L. J.; Sternfeld, F.; Jelley, R. A.; Reeve, A. J.; Carling, R. W.; Moore, K. W.; McKernan, R. M.; Sohal, B.; Cook, S.; Pike, A. J. Med. Chem. 2004, 47, 3642.
13. [13]
  Aly, A. A.; El-Karim, I. A. Phosphorus, Sulfur, Silicon Relat. Elem. 2005, 180, 1997.
14. [14]
  Tarzia, G.; Occelli, E.; Toja, E. J. Med. Chem. 1988, 31, 1115.
15. [15]
  Wu, Y.; Sun, L. P.; Ma, L. X.; Che, J.; Song, M. X. Chem. Biol. Drug Des. 2013, 81. 591
16. [16]
  Duan, Y. C.; Zheng, Y. C.; Li, X. C.; Wang, M. M.; Ye, X. W.; Guan, Y. Y.; Liu, G. Z.; Zheng, J. X.; Liu, H. M. Eur. J. Med. Chem. 2013, 64, 99.
17. [17]
  Vitorovic-Todorovic, M. D.; Eric-Nikolic, A.; Kolundzija, B.; Hamel, E.; Ristic S.; Juranic, I. O.; Drakulic, B. J. Eur. J. Med. Chem. 2013, 62, 40.
18. [18]
  Xue, D. Q.; Zhang, X. Y.; Wang, C. J.; Ma, L. Y.; Zhu, N.; He, P.; Shao, K. P.; Chen, P, J.; Gu, Y, F.; Zhang, X. S.; Wang, C. F.; Ji, C. H.; Zhang, Q. R.; Liu, H. M. Eur. J. Med. Chem. 2014, 85, 235.
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