Comparison of some 3-(substituted-benzylidene)-1,3-dihydroindolin derivatives as ligands of tyrosine kinase based on binding mode studies and biological assay

Arch Pharm Res. 2006 Nov;29(11):1006-17. doi: 10.1007/BF02969285.

Abstract

A series of 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one, 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione and 2, 2'-dithiobis 3-(substituted-benylidene)-1, 3-dihydro-indole derivatives was investigated as inhibitor of p60c-Src tyrosine kinase by performing receptor docking studies and inhibitory activity toward tyrosine phosphorylation. Some compounds were shown to be docked at the site, where the selective inhibitor PP1 [1-tert-Butyl-3-p-tolyl-1H-pyrazolo[3,4-d]pyrimidine-4-yl-amine] was embedded at the enzyme active site. Evaluation of all compounds for the interactions with the parameters of lowest binding energy levels, capability of hydrogen bond formations and superimposibility on enzyme active site by docking studies, it can be assumed that 3-(substituted- benzylidene)-1, 3-dihydro-indolin-2-one and thione derivatives have better interaction with enzyme active site then 2, 2'-dithiobis 3-(substituted-benzylidene)-1, 3-dihydro indole derivatives. The test results for the inhibitory activity against tyrosine kinase by Elisa method revealed that 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione derivatives have more activity then 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one derivatives.

Publication types

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

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Benzylidene Compounds / chemistry*
  • Benzylidene Compounds / pharmacology*
  • Binding Sites / drug effects
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Benzylidene Compounds
  • Enzyme Inhibitors
  • Indoles
  • Ligands
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins pp60(c-src)