In-vitro antiproliferative activities and kinase inhibitory potencies of glycosyl-isoindigo derivatives

Anticancer Drugs. 2007 Oct;18(9):1069-74. doi: 10.1097/CAD.0b013e328182d281.

Abstract

In the course of studies on the preparation of potential kinase inhibitors, we were interested in the synthesis of diversely substituted glycosyl-isoindigo derivatives. To get an insight into the effect of the substitution pattern of the isoindigo aromatic and carbohydrate moieties on the biological activities and to identify the cellular target(s) involved in the in-vitro antiproliferative activity of these derivatives, their inhibitory activities toward a panel of 10 different kinases were examined. The best inhibitory activities were found toward cyclin-dependent kinase 2/cyclin A. Molecular modelling experiments were carried out to investigate the binding interactions between the active site of cyclin-dependent kinase 2 and the lead compound of this series.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Glycosylation
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / chemistry
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Indoles
  • Protein Kinase Inhibitors
  • Protein Kinases