Synthesis and antiproliferative activity of indolizinophthalazine-5,12-dione derivatives, DNA topoisomerase IB inhibitors

Eur J Med Chem. 2010 Sep;45(9):3938-42. doi: 10.1016/j.ejmech.2010.05.048. Epub 2010 Jun 1.

Abstract

A series of novel indolizinophthalazine-5,12-dione derivatives were designed and synthesized by the reaction of 6,7-dichlorophthalazine-5,8-dione with active methylene reagents (AMR) and pyridine derivatives. Some of synthesized compounds exhibited significant in vitro antiproliferative activity at micromolar level toward four human tumor cell lines, including lung adenocarcinoma cell, large-cell lung carcinoma cell, breast carcinoma cell and ardriamycin-resistance breast carcinoma cell. The DNA topoisomerase IB inhibitory assay indicated that DNA topoisomerase IB might be a biological target of the synthesized compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type I / metabolism*
  • Drug Design
  • Humans
  • Indolizines / chemical synthesis*
  • Indolizines / chemistry
  • Indolizines / pharmacology*
  • Inhibitory Concentration 50
  • Nitrogen / chemistry
  • Phthalazines / chemical synthesis*
  • Phthalazines / chemistry
  • Phthalazines / pharmacology*
  • Topoisomerase I Inhibitors / chemical synthesis*
  • Topoisomerase I Inhibitors / chemistry
  • Topoisomerase I Inhibitors / pharmacology*

Substances

  • Indolizines
  • Phthalazines
  • Topoisomerase I Inhibitors
  • DNA Topoisomerases, Type I
  • Nitrogen