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.
Robust QSAR models were obtained using CoMFA and CoMSIA methods that provide a guide to further modification of new tricyclic oxazolidinones.