Synthesis and biological evaluation of new cytotoxic indazolo[4,3-gh]isoquinolinone derivatives

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1846-52. doi: 10.1016/j.bmcl.2013.01.022. Epub 2013 Jan 23.

Abstract

A series of indazolo[4,3-gh]isoquinolinones derivatives have been synthesized to decrease cardiotoxic side effects in comparison to Mitoxantrone. The antiproliferative effects of different side chains were investigated and tested on at least four different cell lines of cervix, ovarian, CNS, NSCLC (non-small-cell lung cancer) and colon carcinoma. In addition to antiproliferative activities, influence on cell cycle and intercalation behavior have been tested.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA / chemistry
  • DNA / metabolism
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Indazoles / chemistry*
  • Mitoxantrone / chemistry
  • Mitoxantrone / toxicity
  • Quinolones / chemical synthesis
  • Quinolones / chemistry*
  • Quinolones / toxicity
  • S Phase Cell Cycle Checkpoints / drug effects
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Indazoles
  • Quinolones
  • DNA
  • Mitoxantrone