Synthesis and antitumor activity of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones

Anticancer Drug Des. 2001 Apr-Jun;16(2-3):167-74.

Abstract

The synthesis of 3-(5-imidazo]2,1-blthiazolylmethylene)-2-indolinones, analogs of compounds recently published, is described. The EIZ isomerism was studied by means of nuclear Overhauser effect experiments and X-ray crystallography. All the compounds were tested as potential antitumor agents. They were also tested as potential inhibitors of cyclin-dependent kinase 1 (CDK1), in order to determine if the antitumor activity was related to this mechanism of action. The results showed that under certain substitution conditions (5-methoxy group for the indole benzene ring and 2-methyl group for the imidazothiazole system), an interesting antitumor activity was found for some compounds. From the analysis of the antitumor data, 3-1(2,6-dimethylimidazo[2,1-bJ-thiazol-5-yl)methylenel-5-methoxy-2-indolinone was the most active of the whole series.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • CDC2 Protein Kinase / antagonists & inhibitors
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Conformation
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Indoles
  • Thiazoles
  • CDC2 Protein Kinase