Article
  • Copolymerization of 1-(2-Carbomethoxy acryloyl)-5-fluorouracil with Vinyl Acetate, Methyl Methacrylate, and Styrene
  • Lee NJ, Ha CS, Cho WJ
  • 1-(2-카르보메톡시아크릴로일)-5-플루오르우라실과 초산비닐, 메틸메타크릴레이트 및 스티렌과의 공중합
  • 이능주, 하창식, 조원제
Abstract
Copolymerizations of 1-(2-carbomethoxyacryloyl)-5-fluorouracil(CMAFU) with vinyl acetate. methyl methacrylate, and styrene were carried out with 2,2'-azobisisobutyronitrile in tetrahydrofuran at 50℃. The copolymer compositions were determined by quantitative infrared(IR) analysis. The monomer reactivity ratios, r1 and r2 were determined by the Kelen-Tudos method. The values of r1 and r2 for each monomer pair were as follows; r1(CMAFU)=0.04 and r2(VAc)=0.19 ; r1 (CMAFU)=0.01 and r2(MMA)=32.11 ; r1(CMAFU)=0.01 and r2(St)=7.65. These values imply that the copolymerizations were significantly affected by the steric hindrance of CMAFU. Toxicity of 5-fluorouracil(5-FU), CMAFU and its copolymers obtained for this work was tested in Drosophila melanogaster. It was observed that the toxicity decreased in the order of 5-FU> copolymer>CMAFU.

1-(2-Carbomethoxyacryloyl)-5-fluorouracil(CMAFU)과 초산비닐(VAc), 메틸메타크릴레이트(MMA) 및 스티렌을 tetrahydrofuran을 용매로 사용하여 50℃에서 라디칼 공중합을 하였다. 공중합체내의 단량체조성은 공중합체의 IR 스펙트럼으로부터 정량분석하여 구하였다. Kelen-Tudos법에 의해 구한 각각의 단량체 반응성비의 값은 r1(CMAFU)= 0.04 r2(VAc)=0.19 ; r1 (CMAFU)=0.01 r2 (MMA)=32.11 ; r1(CMAFU)=0.01과 r2(St)=7.65이었다. 얻어진 단량체 반응성비의 값들로부터 CMAFU와 VAc, MMA 및 St 공중합에서 CMAFU의 입체장애 효과가 큰 영향을 미치는 것을 알 수 있었다. 노랑초파리(Drosophila melanogaster)를 이용하여 5-플루오르우라실(5-FU), 합성한 CMAFU 단량체 및 공중합체들의 독성을 조사한 결과, 5-FU>공중합체>CMAFU순으로 독성이 감소하였다.

References
  • 1. Donaruma LGAnionic Polymeric Drugs, L.G. Donaruma, R.M. Ottenbrite and O. Vogl, Eds., John Wiley & Sons, Icn., New York, Vol. 1, p. 50 (1980)
  •  
  • 2. Merigan TC, Regelson W, N. Engl. J. Med., 277, 1283 (1967)
  •  
  • 3. Morahan PS, Regelson W, Munson AEAntimicrobiological Agents and Chemotheraphy, p. 16 (1972)
  •  
  • 4. Ottenbrite RMThe Antitumor and Antiviral Effects of Polycarboxylic Acid Polymers, in biological Activities of Polymers, ACS Symposium Series 186, Amer. Chem. Soc., Washington, D.C. (1982)
  •  
  • 5. Ottenbrite RM, Goodell E, Munson A, Polymer, 18, 461 (1977)
  •  
  • 6. Butler GB, J. Macromol. Sci.-Rev. Macromol. Chem. Phys., C22, 89 (1982)
  •  
  • 7. Breslow DS, Pure Appl. Chem., 46, 103 (1979)
  •  
  • 8. DcClereq E, Merigan TC, Arch. Int. Med., 126, 94 (1970)
  •  
  • 9. Mohr SJ, Chirigos MA, Fuhrman FS, Pryor JW, Cancer Res., 35, 3750 (1975)
  •  
  • 10. Regelson W, Munson A, Wooles WInternational Symposium on Standards of Interferon and Interferon Inducers, London (1969)
  •  
  • 11. Regelson W, Munson A, Wooles WSymposium Series Immunobiological Standards, Vol. 14, Korger, Basel, p. 227 (1970)
  •  
  • 12. Roberts PS, Regelson W, Kingsbury B, J. Lab. Clin. Med., 2, 822 (1973)
  •  
  • 13. Han MJ, Lee DH, Lee WY, Hahn BS, Bull. Korean Chem. Soc., 10, 212 (1989)
  •  
  • 14. Han MJ, Kang SD, Lee WY, Bull. Korean Chem. Soc., 11, 154 (1990)
  •  
  • 15. Han MJ, Choi KB, Kim KH, Cho TJ, Lee WY, Shim WN, J. Bioactive Compatible Polym., 5, 420 (1990)
  •  
  • 16. Akashi M, Tanaka Y, Miyazaki T, Miyauchi N, J. Bioactive Compatible Polym., 2, 120 (1987)
  •  
  • 17. Lewis EB, Bacher F, Dorosophila Inform. Ser., 43, 193 (1968)
  •  
  • 18. Duschinsky R, Gabrel TFU.S. Patent, No. 3,354,160 (1967)
  •  
  • 19. Umrigar PP, Ohashi S, Butler GB, J. Polym. Sci. A: Polym. Chem., 17, 351 (1979)
  •  
  • 20. Cho WJPh.D. Dissertation, University of Paris VI (1978)
  •  
  • 21. Das S, Rodriguez F, J. Appl. Polym. Sci., 39, 1309 (1990)
  •  
  • 22. Kelen T, Tudos F, J. Macromol. Sci.-Chem., A9, 1 (1975)
  •  
  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2023 Impact Factor : 0.4
  • Indexed in SCIE

This Article

  • 1991; 15(2): 211-217

    Published online Apr 25, 1991