Naphthazarin derivatives (II): formation of glutathione conjugate, inhibition of DNA topoisomerase-I and cytotoxicity

Bioorg Med Chem Lett. 1999 Aug 16;9(16):2407-12. doi: 10.1016/s0960-894x(99)00397-2.

Abstract

6-(1-Hydroxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones, expressing a higher reactivity in conjugation with glutathione, showed a greater potency in the inhibition of DNA topoisomerase-I and the cytotoxicity against L1210 cells than 2-(1-hydroxyalkyl)-DMNQ derivatives, implying the participation of electrophilic arylation in the bioactivities. In further study 6-(1-Hydroxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones with an alkyl group of shorter chain length (C2-C6) exerted a greater bioactivities than those with longer chain length(>C6).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Glutathione / chemistry*
  • Leukemia L1210 / pathology*
  • Naphthoquinones / chemistry*
  • Naphthoquinones / pharmacology
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Naphthoquinones
  • Topoisomerase I Inhibitors
  • naphthazarin
  • Glutathione