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Synthesis of 3-Alkylthio-6-Allylthiopyridazine Derivatives and Their Antihepatocarcinoma Activity

Kwon Soon-Kyoung    (College of Pharmacy, Duksung Women's University   ); Moon Aree    (College of Pharmacy, Duksung Women's University  );
  • 초록

    The allylthio group of allicin and other organosulfur compounds, isolated from garlic, is considered a pharmacophore, and a key structure component of the molecule, which affords biological activities. In the foregoing studies, various 3-alkoxy-6-allylthiopyridazine derivatives (K­compounds) were synthesized, and their biological activities tested in animals. As expected, the various derivatives showed good hepatoprotective activities on carbon tetrachloride-treated mice and aflatoxin B1-treated rats, and chemopreventive activities on hepatocarcinoma cells in rats. Other new pyridazine derivatives, with the oxygen atom at the 3-position of the 3-alkoxy­6-allylthiopyridazine displaced by sulfur (S), were synthesized, and their activities tested in vitro. Thio-K6, one of the sulfur-substituted compounds, showed better chemopreventive activity toward hepatocarcinoma cells.


  • 주제어

    Pyridazine .   Allylthiopyridazine .   Allicin .   Organosulfur compounds .   K-6 .   K-16 .   K-17 .   Thio-K Compound .   Antihepatocarcinoma .   Chemopreventive.  

  • 참고문헌 (26)

    1. Chai, H. Y. Sin, J. S. Moon, A. R., Kwon, S. K. and Kang, J. K. et al., Antitumor activity of pyridazine derivative in nude mice. Kor. J. Lab. Animal Sci., 20. 68-75 (2004) 
    2. Cavallito, C. J. and Bailey, J. H. and Buck, J. S., Antibacterial principle of Allium sativum. III. Its precursor and 'essential oil of garlic'. J. Am. Chem. Soc., 67, 1032 - 1033 (1945) 
    3. Fenwick, G. R. and Hanley, A. B. The genus Allium--Part 3. Crit. Rev. Food Sci. Nutr., 23, 1-73 (1985) 
    4. Tsao, S. M. and Yin, M. C., In vitro activity of garlic oil and four diallylsulfides against antibiotic resistant Pseudomonas aeruginosa and Klebsiella pneumoniae. J. Antimicrob. Chemother., 47, 665-670 (2001a) 
    5. Wertheim, T., Investigation of garlic oil. Ann., 51, 289-301 (1844) 
    6. Shin, H. S. and Kwon, S. K., Hepatoprotective effects of synthetic 3-alkoxy-6-allylthiopyridazine derivatives on aflatoxin B1-induced chronic or acute toxicity. Duksung Women's University J., 32, 175-185 (2003b) 
    7. Kwon, S. K., Lee, E. B., Kim, M. K. and Park, Y. N., Synthesis of allylthiopyridazine derivatives and hepatoprotective activities. Duksung Bull. Pharm. Sci., 9, 3-13 (1998) 
    8. Kwon, S. K. and Kim, M. K., Synthesis of aryloxyallylthiopyridazine derivatives. Yakhak Hoeji, 46, 89-92 (2002a) 
    9. Block, E., The chemistry of garlic and onions. Scientific American, 252, 94-99 (1985) 
    10. Lee, J. I., Park, H,, Yun, Y. S. and Kwon, S. K., An efficient synthesis of 3-alkoxy-6-allylthiopyridazine. J. Kor. Chem. Soc., 45, 386-390 (2001) 
    11. Kwon, S. K., Organosulfur compounds from Allium sativum and physiological activities. J. Appl. Pharm., 11, 8-32 (2003) 
    12. O'Gara, E. A., Hill, D. J. and Maslin, D. J., Activities of garlic oil, garlic powder, and their diallyl constituents against Helicobacter pylori. Appl. Environ. Microbiol., 66, 2269-2273 (2000) 
    13. Kwon, S. K. and Seoul Pharm. Co., Allylthiopyridazine derivatives and process for preparing the same. US Patent, 5,942,511 (1999) 
    14. Shin, H. S. and Kwon, S. K., Synthesis of allylthiopyridazine derivatives and inhibition of aflatoxin B1-induced hepatotoxicity in rats. Arch. Pharm. Res., 26, 351-357 (2003a)     
    15. Shin, H. S. and Kwon, S. K., Protective effects of synthetic allylthiopyridazine derivatives on carbon tetrachlorideinduced hepatotoxicity. Dukung Bull. Pharm. Sci., 13, 47-50 (2002) 
    16. Semmler, F. W., Das aetherische Oel des Kuchenzwiebels. Arch. Pharm., 230, 443-448 (1892b) 
    17. Lee, E. J., Shin, I. C., Kwon, S. K., Shin, H. S. and Moon, A. R., Chemopreventive allylthiopyridazines inhibit invasion, migration and angiogenesis in hepatocarcinoma cells. Int. J. Oncol., 23, 1645-1650 (2003) 
    18. Van de Loosdrecht, A. A., Beelen, R. H., Ossenkoppele, G. J., Broekhoven, M. G. and Langenhuijsen, M. M., A tetrazoliumbased colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia. J. Immunol. Methods, 174, 311-320 (1994) 
    19. Cavallito, C. J., Buck, J. S. and Suter, C. M., Allicin, the antibacterial principle of Allium sativum. II. Determination of the chemical structure. J. Am. Chem. Soc., 66, 1952-1954 (1944b) 
    20. Cavallito, C. J. and Bailey, J. H., Allicin, the antibacterial principle of Allium sativum. I. Isolation, Physical properties and antibacterial action. J. Am. Chem. Soc., 66, 1950-1951 (1944a) 
    21. Kwon, S. K., Synthesis of 4,5-substituted 3-alkoxyy-6-allylthiopyridazine derivatives. Yakhak Hoeji, 46, 155-160 (2002b) 
    22. Ferrari, M., Fornasiero, M. C. and Isetta, A. M., MTT colorimetric assay for testing macrophage cytotoxic activity in vitro. J. Immunol. Methods, 131, 165-172 (1990) 
    23. Semmler, F. W., Ueber das aetherische Oel des Knobrauchs. Arch. Pharm., 230, 434-443 (1892a) 
    24. Jung, M. Y., Kwon, S. K. and Moon, A. R., Chemopreventive allylthiopyridazine derivatives induce apoptosis in SK-Hep-1 hepatocarcinoma cells through a caspase-3-dependent mechanism. Eur. J. Cancer., 37, 2104-2110 (2001) 
    25. Kwon, S. K. and Seoul Pharm. Co., Novel allylthiopyridazine derivatives and process for preparing the same. European Patent, 1,058,681 (2003) 
    26. Tsao, S. M. and Yin, M. C., In vitro antimicrobial activity of four diallyl sulfides occurring naturally in garlic and Chinese leek oils. J. Med. Microbiol., 50, 646-649 (2001b) 
  • 이 논문을 인용한 문헌 (1)

    1. 2010. "" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea, 33(2): 189~196     

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