Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic oxazolidinones as antibacterial agents

Bioorg Med Chem. 2003 Jun 12;11(12):2569-74. doi: 10.1016/s0968-0896(03)00157-3.

Abstract

Oxazolidinones exemplified by eprezolid and linezolid are a new class of antibacterials that are active against Gram positive and anaerobic bacteria including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and vancomycin resistant enterococci (VRE). In an effort to have a better antibacterial agent in the oxazolidinone class, we have performed three-dimensional quantitative structure-activity relationship (3D-QSAR) studies for a series of tricyclic oxazolidinones. 3D-QSAR studies were performed using the Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) procedures. These studies were performed using 42 compounds; the QSAR model was developed using a training set of 33 compounds. The predictive ability of the QSAR model was assessed using a test set of 9 compounds. The predictive 3D-QSAR models have conventional r(2) values of 0.975 and 0.940 for CoMFA and CoMSIA respectively; similarly, cross-validated coefficient q(2) values of 0.523 and 0.557 for CoMFA and CoMSIA, respectively, were obtained. The CoMFA 3D-QSAR model performed better than the CoMSIA model.

MeSH terms

  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / pharmacology*
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Oxazolidinones / chemistry*
  • Oxazolidinones / pharmacology*
  • Quantitative Structure-Activity Relationship
  • Staphylococcus aureus / drug effects
  • Static Electricity

Substances

  • Anti-Infective Agents
  • Oxazolidinones