Citation: Jun-Peng Zhang, Jie Huang, Chao Liu, Xu-Fang Lu, Bao-Xiang Wu, Li Zhao, Na Lu, Qing-Long Guo, Zhi-Yu Li, Cheng Jiang. Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors[J]. Chinese Chemical Letters, ;2014, 25(7): 1025-1028. doi: 10.1016/j.cclet.2014.05.048 shu

Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors

Jun-Peng Zhang ^a,b,c ,
Jie Huang ^d ,
Chao Liu ^a,b,c ,
Xu-Fang Lu ^a,b,c ,
Bao-Xiang Wu ^a,b,c ,
Li Zhao ^c ,
Na Lu ^c ,
Qing-Long Guo ^c ,
Zhi-Yu Li ^a,b,c,, ,
Cheng Jiang ^a,b,c,,

1.
a Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;
2.
b Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China;
3.
c Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China;
4.
d Gansu Institute for Food and Drug Control, Lanzhou 730070, China

Corresponding author: Zhi-Yu Li, Cheng Jiang,
Received Date: 25 March 2014
Available Online: 27 May 2014
Fund Project: This work was supported by the National Natural Science Foundation of China (No. 21072232) (No. 21072232) the Fundamental Research Funds for the Central Universities (No. JKZ2011002) (No. JKZ2011002)

A series of new 3-benzoheterocyclic substituted pyridopyrimidines were designed and synthesized. Structures of the compounds were determined by IR, ¹H NMR, and elemental analyses. The antiproliferation activity of 13 novel compounds was evaluated in A549, HL-60, BGC-823 and SMMC-7721 cell lines. Compounds 3, 5, 7, 8, 9, 10 showed potent inhibitory activity against the four tested cancer cell lines. These six compounds were examined for Top I inhibition at 100 mmol/L by measuring the relaxation of supercoiled DNA in plasmid pBR322. Most of the tested compounds inhibited the enzyme at this concentration. The most potent compound 9 was as potent as camptothecin.
- Topoisomerase I inhibitors,
- Pyridopyrimidine,
- Anticancer,
- Synthesis
1. [1]
  [1] L.F. Liu, DNA topoisomerase poisons as antitumor drugs, Annu. Rev. Biochem. 58 (1989) 351-375.
2. [2]
  [2] B.K. Sinha, Topoisomerase inhibitors. A review of their therapeutic potential in cancer, Drugs 49 (1995) 11-19.
3. [3]
  [3] B.M. Fox, X. Xiao, S. Antony, et al., Design, synthesis, and biological evaluation of cytotoxic 11-alkenylindenoisoquinoline topoisomerase I inhibitors and indenoisoquinoline-camptothecin hybrids, J. Med. Chem. 46 (2003) 3275-3282.
4. [4]
  [4] A. Morrell, S. Antony, G. Kohlhagen, et al., A systematic study of nitrated indenoisoquinolines reveals a potent topoisomerase I inhibitor, J. Med. Chem. 49 (2006) 7740-7753.
5. [5]
  [5] Y. Pommier, Topoisomerase I inhibitors: camptothecins and beyond, Nat. Rev. Cancer 6 (2006) 789-802.
6. [6]
  [6] X.S. Xiao, S. Antony, Y. Pommier, et al., Total synthesis and biological evaluation of 22-hydroxyacuminatine, J. Med. Chem. 49 (2006) 1408-1412.
7. [7]
  [7] Z.Y. Li, F.M. Zhai, L. Zhao, et al., Design and synthesis of N-methylmaleimide indolocarbazole bearing modified 2-acetamino acid moieties as Topoisomerase I inhibitors, Bioorg. Med. Chem. Lett. 19 (2009) 406-409.
8. [8]
  [8] X.Y. Zhang, R. Wang, L. Zhao, et al., Synthesis and biological evaluations of novel indenoisoquinolinesas topoisomerase I inhibitors, Bioorg. Med. Chem. Lett. 22 (2012) 1276-1281.
9. [9]
  [9] Y. Pommier, DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition, Chem. Rev. 109 (2009) 2894-2902.
10. [10]
  [10] Q.D. You, Z.Y. Li, C.H. Huang, et al., Discovery of a novel series of quinolone and naphthyridine derivatives as potential topoisomerase I inhibitors by scaffold modification, J. Med. Chem. 52 (2009) 5649-5661.
11. [11]
  [11] M.M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem. 72 (1976) 248-254.
12. [12]
  [12] E. Aflalo, S. Iftach, S. Segal, et al., Inhibition of topoisomerase I activity by tyrphostin derivatives, protein tyrosine kinase blockers: mechanism of action, Cancer Res. 54 (1994) 5138-5142.
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