A novel indeno[1,2-b]pyridinone derivative, a DNA intercalative human topoisomerase IIα catalytic inhibitor, for caspase 3-independent anticancer activity

Chem Commun (Camb). 2017 Jun 22;53(51):6864-6867. doi: 10.1039/c7cc02372c.

Abstract

A novel 2-(furan-2-yl)-4-(pyridin-2-yl)-5H-indeno[1,2-b]pyridin-5-one (TI-1-190) was synthesized using a simple microwave-assisted method and its mode of action was systematically characterized. It is a DNA intercalative human topoisomerase IIα catalytic inhibitor with much stronger activity and less DNA toxicity than etoposide, a topoisomerase II poison. TI-1-190 displays caspase 3-independent anticancer activity, unlike etoposide.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Biocatalysis
  • Caspase 3* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type II / metabolism
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Intercalating Agents / chemical synthesis
  • Intercalating Agents / chemistry
  • Intercalating Agents / pharmacology*
  • MCF-7 Cells
  • Molecular Structure
  • Poly-ADP-Ribose Binding Proteins / antagonists & inhibitors*
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors / chemical synthesis
  • Topoisomerase II Inhibitors / chemistry
  • Topoisomerase II Inhibitors / pharmacology*

Substances

  • Antineoplastic Agents
  • Intercalating Agents
  • Poly-ADP-Ribose Binding Proteins
  • Topoisomerase II Inhibitors
  • Caspase 3
  • DNA Topoisomerases, Type II
  • TOP2A protein, human