Three-dimensional quantitative structure-activity relationship studies on c-Src inhibitors based on different docking methods

Chem Biol Drug Des. 2009 Apr;73(4):416-27. doi: 10.1111/j.1747-0285.2009.00789.x.

Abstract

c-Src kinase play an important role in cell growth and differentiation and its inhibitors can be useful for the treatment of various diseases, including cancer, osteoporosis, and metastatic bone disease. Three dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on quinazolin derivatives inhibiting c-Src kinase. Molecular field analysis (MFA) models with four different alignment techniques, namely, GLIDE, GOLD, LIGANDFIT and Least squares based methods were developed. glide based MFA model showed better results (Leave one out cross validation correlation coefficient r(2)(cv) = 0.923 and non-cross validation correlation coefficient r(2)= 0.958) when compared with other models. These results help us to understand the nature of descriptors required for activity of these compounds and thereby provide guidelines to design novel and potent c-Src kinase inhibitors.

Publication types

  • Comparative Study

MeSH terms

  • CSK Tyrosine-Protein Kinase
  • Catalytic Domain
  • Computer Simulation
  • Crystallography, X-Ray
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Protein Binding
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / metabolism*
  • Quantitative Structure-Activity Relationship
  • Quinazolines / chemistry*
  • Quinazolines / metabolism*
  • src-Family Kinases

Substances

  • Ligands
  • Quinazolines
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human