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Naphthazarin derivatives (V): Formation of glutathione conjugate and cytotoxic activity of 2-or 6-substituted 5,8-dimethoxy-1,4-napthoquinones in the presence of glutathione-S-transferase, in rat liver S-9 fraction and mouse liver perfusate

  • Xiang-Guo Zheng
  • Jong-Seong Kang
  • Hwan-Mook Kim
  • Guang-Zhu Jin
  • Byung-Zun Ahn
Research Articles Medicinal Chemistry & Natural Products

Abstract

Formation of glutathione (GSH) conjugates with 2- or 6-(1-hydroxymethyl)- and 2-(1-hydroxyethyl)-DMNQ derivatives (DMNQ, 5,8-dimethoxy-1,4-naphthoquone) was carried out in phosphate buffer (pH 7.4), in the presence of glutathione-S-transferase (GST), in rat liver S-9 fraction and by perfusion, and the rates of conjugates formation were compared and correlated to cytotoxicity. The GSH conjugates of 6-(1-hydroxyalkyl)-DMNQ derivatives were formed faster than 2-(1-hydroxyalkyl)-DMNQ derivatives under all of the media, implying that steric hindrance was the cause of lowering the rate of conjugate formation of 2-substituted derivatives. For both isomers, addition of GST did not improve the reaction rate, compared with that in buffer, while the reaction in the S-9 fraction and the perfusate was accelerated to a great extent. The catalytic effect of the S-9 fraction and the perfusion on 2-isomers was greater than on 6-substituted ones, suggesting that S-9 fraction and the perfusate contain an effective system relaxing the steric hindrance of 2-(1-hydroxyalkyl)-DMNQ derivtives. Furthermore, a good correlation between the formation of the GSH conjugates and the cytotoxic activity of both naphthazarin isomers suggests that the steric hindrance is a cause of lowering the cytotoxicity of 2-isomers.

Key words

Naphthazarin derivatives Formation of glutathione conjugates Glutathione-S-transferase Rat liver S-9 fraction Mouse liver perfusion 

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Copyright information

© The Pharmaceutical Society of Korea 1999

Authors and Affiliations

  • Xiang-Guo Zheng
    • 1
  • Jong-Seong Kang
    • 1
  • Hwan-Mook Kim
    • 2
  • Guang-Zhu Jin
    • 3
  • Byung-Zun Ahn
    • 1
  1. 1.College of PharmacyChungnam National UniversityTaejonKorea
  2. 2.Korea Research Institute for Biology and BiotechnologyKorea
  3. 3.College of PharmacyYanbian UniversityJanji, JilinChina

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