Quinoline-carboxylic acids are potent inhibitors that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins

Bioorg Med Chem Lett. 2003 Jun 2;13(11):1931-4. doi: 10.1016/s0960-894x(03)00322-6.

Abstract

4-benzylquinolines 5, based on a series of isoquinolines 1, were prepared and tested as inhibitors of the IGF/IGFBP-3 complex based on their ability to displace IGF-I from its binding to IGF-binding protein-3. SAR studies on the 6,7-dihydroxy moiety of the quinoline 5a showed that the catecol moiety could be replaced with other functional groups. Computational modeling of the 5a/mini-IGFBP-5 complex revealed the possible binding site of 5a on IGFBP-5.

MeSH terms

  • Acids, Carbocyclic / chemistry*
  • Acids, Carbocyclic / pharmacology*
  • Amino Acid Sequence
  • Binding Sites
  • Binding, Competitive
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / antagonists & inhibitors*
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor Binding Protein 5 / genetics
  • Insulin-Like Growth Factor Binding Protein 5 / metabolism
  • Insulin-Like Growth Factor I / antagonists & inhibitors*
  • Insulin-Like Growth Factor I / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Acids, Carbocyclic
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Protein 5
  • Quinolines
  • Insulin-Like Growth Factor I