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Syntheses and evaluations of antitumor and antiangiogenic phthalate polymers containing 5-fluorouracil and carboxylates

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Abstract

New antitumor active polymers, poly(methacryloyl-2-oxy-1,2,3-propanetricarboxylic acid-co-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic acid) [poly(MTCA-co-ETAc)], poly(methacryloyl-2-oxy-1,2,3-propanetricarboxylic acid-co-hydrogen ethyl-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalate) [poly(MTCA-co-HEET)], and poly (methacryloyl-2-oxy-1,2,3-propanetricarboxylic acid-co-a-ethoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil) [poly(MTCA-co-EETFU)] were synthesized and characterized. Their antitumor activity, inhibition of DNA replication and antiangiogenesis were examined. The structures of the polymers were identified by FT-IR,1H and13C-NMR spectroscopy. The number average molecular weights of the fractionated polymers determined by GPC ranged from 9,400 to 14,900, and polydispersity indices were less than 1.7. Thein vitro cytotoxicity of these polymers was determined and their antitumor activity was evaluated. The IC50 values (the drug concentration at inhibition of 50% tumor growth) indicated that the synthesized polymers were much better inhibitors of cancer cells and showed lower cytotoxicity than the free 5-FU. Thein vivo antitumor activity of the conjugates was examined using mice bearing the sarcoma 180 tumor cell line. The life spans (T/C) of the mice treated with the conjugates were higher than those treated with the free 5-FU. In addition, the synthesized conjugates showed excellent antiangiogenic activity based on an embryo chorioallantoic membrane assay.

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References

  1. G. B. Butler,J. Polym. Sci.,48, 279 (1969).

    Article  Google Scholar 

  2. G. B. Butler and A. Zampini,J. Macromol. Sci. Chem.,A11, 491 (1977).

    CAS  Google Scholar 

  3. S. Ozaki, Y. Ike, H. Mizuni, K. Ishikawa, and H. Mori,Bull. Chem. Soc.,50, 2406 (1977).

    Article  CAS  Google Scholar 

  4. M. Akashi, N. Miyauchi, N. Morita, and T. Minota,J. Bioactive Compatible Polym.,2, 232 (1987).

    Article  CAS  Google Scholar 

  5. I. D. Chung, C. S. Ha, J. K. Lee, C. K. Lee, and D. Xie,Macromol. Res.,14, 668 (2006).

    Article  CAS  Google Scholar 

  6. I. D. Chung, C. K. Lee, C. S. Ha, and W. J. Cho,J. Polym. Sci. Part A: Polym. Chem.,44, 295 (2006).

    Article  CAS  Google Scholar 

  7. J. W. Bae, D. H. Go, and K. D. Park,Macromol. Res.,14, 461 (2006).

    Article  CAS  Google Scholar 

  8. S. H. Cho and K. S. Kim,Macromol. Res.,11, 317 (2003).

    Article  CAS  Google Scholar 

  9. W. J. Cho and C. S. Ha,Polymer Materials Encyclopedia: Synthesis Properties and Application,1, 357 (1996).

    Google Scholar 

  10. W. M. Choi, N. J. Lee, Y. W. Lee, C. S. Ha, and W. J. Cho,Macromol. Symp.,118, 616 (1997).

    Google Scholar 

  11. W. M. Choi, N. J. Lee, C. S. Ha, and W. J. Cho,Polym. Int.,43, 167 (1997).

    Article  CAS  Google Scholar 

  12. J. G. Park, W. M. Choi, N. J. Lee, C. S. Ha, and W. J. Cho,J. Polym. Sci. Part A: Polym. Chem.,36, 1625 (1998).

    Article  CAS  Google Scholar 

  13. W. M. Choi, I. D. Chung, N. J. Lee, Y. W. Lee, C. S. Ha, and W. J. Cho,J. Polym. Sci. Part A: Polym. Chem.,36, 2177 (1997).

    Article  Google Scholar 

  14. I. D. Chung, E. Y. Jung, Y. W. Lee, S. H. Kim, C. S. Ha, and W. J. Cho,J. Polym. Sci. Part A: Polym. Chem.,38, 4272 (2000). Figure 3. Optical microphotographs of control (I), MTCA (II), EETFU (III), poly(MTCA-co-ETAc) (IV), poly(MTCA-co-HEET) (V), and poly(MTCA-co-EETFU) (VI) on embryonic angiogenesis in CAM (× 100). S.-M. Leeet al. 516Macromol. Res., Vol. 16, No. 6, 2008

    Article  CAS  Google Scholar 

  15. N. J. Lee, I. C. Jeong, M. Y. Cho, C. W. Jeon, B. C. Yun, Y. O. Kim, S. H. Kim, and I. D. Chung,Eur. Polym. J.,42, 3352 (2006).

    Article  CAS  Google Scholar 

  16. S. M. Lee, W. M. Choi, C. S. Ha, and W. J. Cho,J. Polym. Sci. Part A: Polym. Chem.,37, 2619 (1999).

    Article  CAS  Google Scholar 

  17. M. S. Shim, N. J. Lee, C. S. Ha, and W. J. Cho,Polymer (Korea),15, 489 (1991).

    CAS  Google Scholar 

  18. G. T. Gam, J. G. Jeong, N. J. Lee, Y. W. Lee, C. S. Ha, and W. J. Cho,J. Appl. Polym. Sci.,57, 219 (1995).

    Article  CAS  Google Scholar 

  19. E. Y. Jung, I. D. Chung, N. J. Lee, C. S. Ha, and W. J. Cho,J. Polym. Sci. Part A: Polym. Chem.,38, 1247 (2000).

    Article  CAS  Google Scholar 

  20. W. M. Choi, I. D. Chung, N. J. Lee, S. H. Kim, C. S. Ha, and W. J. Cho,Polym. Adv. Technol.,8, 701 (1997).

    Article  CAS  Google Scholar 

  21. S. M. Lee, I. D. Chung, N. J. Lee, C. H. Lee, C. S. Ha, and W. J. Cho,Polym. Int.,50, 119 (2001).

    Article  CAS  Google Scholar 

  22. C. R. Wobbe, F. B. Dean, L. Weissbach, and J. Hurwitz,Proc. National Academy Sci. USA,82, 5710 (1995).

    Article  Google Scholar 

  23. T. Mosmann,J. Immunol. Method,65, 55 (1985).

    Article  Google Scholar 

  24. T. Oikawa, M. Hasegawa, M. Shimamura, H. Ashino-Fuge, and S.I. Murota,Cancer Lett.,48, 157 (1991).

    Article  Google Scholar 

  25. K. W. Fett, D. J. Strydol, R. R. Lobb, E. M. Alderman, J. L. Bethune, L. F. Riordan, and B. L. Callee,Biochemistry,24, 5480 (1985).

    Article  CAS  Google Scholar 

  26. R. Crum, S. Szabo, and J. Folkman,Science,230, 1375 (1985).

    Article  CAS  Google Scholar 

  27. R. M. Ottenbrite,J. Macromol. Sci. Chim.,A22, 819 (1985).

    Article  CAS  Google Scholar 

  28. J. Folkman,J. Mol. Med.,1, 120 (1995).

    Google Scholar 

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Authors and Affiliations

  1. Depart of Polymer Science & Engineering, Pusan National University, 609-735, Busan, Korea

    Sun-Mi Lee, Sangwook Jung, Chang-Sik Ha & Il doo Chung

  2. Division of Life Science, Korea Institute of Science and Technology, 130-650, Seoul, Korea

    Sun-Mi Lee

  3. Division of Chemical Engineering, Pukyong National University, 608-739, Busan, Korea

    Won-Ki Lee

  4. School of Materials Science and Engineering, Pusan National University, 609-735, Busan, Korea

    Yong-Ho Park

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  1. Sun-Mi Lee
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  2. Sangwook Jung
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  3. Chang-Sik Ha
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  4. Il doo Chung
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  5. Won-Ki Lee
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  6. Yong-Ho Park
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Correspondence to Il doo Chung.

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Lee, SM., Jung, S., Ha, CS. et al. Syntheses and evaluations of antitumor and antiangiogenic phthalate polymers containing 5-fluorouracil and carboxylates. Macromol. Res. 16, 510–516 (2008). https://doi.org/10.1007/BF03218552

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  • DOI: https://doi.org/10.1007/BF03218552

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