Synthesis and biological evaluation of 3-(substituted-benzylidene)-1,3-dihydro-indolin derivatives as human protein kinase CK2 and p60(c-Src) tyrosine kinase inhibitors

Biol Pharm Bull. 2007 Apr;30(4):715-8. doi: 10.1248/bpb.30.715.

Abstract

Human protein kinase CK2 is an ubiquitous serine/threonine kinase that is typically found in tetrameric complexes consisting of two catalytic (alpha and/or alpha') and two regulatory beta subunits. Although there is growing evidence that besides the participation of CK2 in a complex series of cellular functions, this protein kinase is involved in cell viability, cell proliferation, and neoplastic transformation. In the present study, a series of 3-(substituted-benzylidene)-1,3-dihydro-indolin-2-thione derivatives and the corresponding indolin-2-one congeners were tested for their inhibition of human recombinant protein kinase CK2 in vitro. The efficacy of these compounds was compared with their inhibitory results of p60(c-Src) tyrosine kinase. It was found that 3-(substituted-benzylidene)-1,3-dihydro-indolin-2-thione derivatives are more effective than indolin-2-one congeners for the inhibition of CK2 and p60(c-Src) tyrosine kinase.

Publication types

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

MeSH terms

  • Benzylidene Compounds / chemistry*
  • Casein Kinase II / antagonists & inhibitors*
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism
  • Evaluation Studies as Topic
  • Humans
  • Indoles / chemical synthesis
  • Indoles / metabolism
  • Indoles / pharmacology*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Recombinant Proteins / antagonists & inhibitors
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Benzylidene Compounds
  • Indoles
  • Protein Kinase Inhibitors
  • Recombinant Proteins
  • Proto-Oncogene Proteins pp60(c-src)
  • Casein Kinase II