3D-QSAR analysis of conformationally constrained diacylglycerol (DAG) analogues as potent protein kinase C (PK-C) ligands

Bioorg Med Chem. 2004 May 15;12(10):2639-44. doi: 10.1016/j.bmc.2004.03.016.

Abstract

A study of the quantitative structure activity relationships (QSARs) was performed based on the binding affinity (pKi) values of 32 protein kinase C (PK-C) ligands. The QSAR study was carried out by using both three-dimensional descriptors (the steric and electrostatic CoMFA fields) and the physicochemical properties (logP values). The CoMFA analysis provided a reasonable QSAR model, with a cross-validated q2 value of 0.671 and a conventional r2 value of 0.956, which was confirmed by the satisfactory prediction of the experimental binding affinity (pKi) values for a series of 3-alkylidene-5,5-disubstituted tetrahydro-2-furanones included in the test set. The resultant QSAR model will be useful for designing highly potent and selective PK-C ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diglycerides / chemistry*
  • Diglycerides / metabolism
  • Ligands
  • Molecular Conformation
  • Protein Binding
  • Protein Kinase C / chemistry
  • Protein Kinase C / metabolism*
  • Quantitative Structure-Activity Relationship
  • Static Electricity

Substances

  • Diglycerides
  • Ligands
  • Protein Kinase C