Dual IGF-1R/SRC inhibitors based on a N'-aroyl-2-(1H-indol-3-yl)-2-oxoacetohydrazide structure

Eur J Med Chem. 2011 Jul;46(7):2759-69. doi: 10.1016/j.ejmech.2011.03.065. Epub 2011 Apr 6.

Abstract

The N'-aroyl-2-(1H-indol-3-yl)-2-oxoacetohydrazide motif was identified as a novel scaffold for the development of kinase inhibitors. Derivatives with a biphenyl element attached to the hydrazide structure proved to be submicromolar dual inhibitors of the cancer-related kinases IGF-1R and SRC. One of the most potent kinase inhibitors of the series produced a selective growth inhibition in a panel of cultivated cancer cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Biphenyl Compounds / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Hydrazines / chemical synthesis*
  • Hydrazines / pharmacology
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / chemistry
  • Structure-Activity Relationship
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / chemistry

Substances

  • Antineoplastic Agents
  • Biphenyl Compounds
  • Hydrazines
  • Indoles
  • Protein Kinase Inhibitors
  • Receptor, IGF Type 1
  • src-Family Kinases