Synthesis and biological evaluations of novel indenoisoquinolines as topoisomerase I inhibitors

Bioorg Med Chem Lett. 2012 Jan 15;22(2):1276-81. doi: 10.1016/j.bmcl.2011.10.019. Epub 2011 Oct 24.

Abstract

A series of novel indenoisoquinoline derivatives were synthesized. The anticancer activities of these molecules were tested in human cancer cell lines A549, HepG2, and HCT-116. These compounds were also tested for their activity of topoisomerase I (top1) inhibition. Among them, compound 25 was found to be 10-times more potent in cell-killing activity for both cell lines HepG2 and HCT-116 than reported compound 11, with IC(50) of 0.019 and 0.093μM, respectively. Compound 25 was also found to have stronger top1 inhibition activity than 11 in our inhibition assay. Further in vivo evaluations of compound 25 are in progress and will be reported in due course.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type I / metabolism
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology*
  • Molecular Structure
  • Stereoisomerism
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors / chemical synthesis*
  • Topoisomerase I Inhibitors / chemistry
  • Topoisomerase I Inhibitors / pharmacology*

Substances

  • Antineoplastic Agents
  • Isoquinolines
  • Topoisomerase I Inhibitors
  • DNA Topoisomerases, Type I