Three-dimensional quantitative structure-activity relationship (3D-QSAR) of 3-aryloxazolidin-2-one antibacterials

Three-dimensional quantitative structure-activity relationship (3D-QSAR) st udies for 3-aryloxazolidin-2-one antibacterials were performed using the ge netic function approximation algorithm. This study was performed using 60 c ompounds, in which the QSAR models were developed using a training set of 5 0 compounds, The in vitro minimum inhibitory concentration (MIC) against St aphylococcus aureus SFCO-1a was used for the study. The predictive ability of the QSAR model was evaluated by using a test set of 10 compounds. The st atistical quality of the QSAR models was assessed using statistical paramet ers r(2), r(ev)(2) (cross-validated r(2)), r(pred)(2) (predictive r(2)) and lack of fit measure (LOF). The results obtained indicate that the antibact erial activity of the 3-aryloxazolidin-2-ones is strongly dependent on elec tronic factor as expressed by lowest unoccupied molecular orbital energy (L UMO), spatial factor as expressed by density and thermodynamic factors acco unted for by molar refractivity and heat of Formation. The model is present ly being used to design and predict new potent molecules prior to synthesis . (C) 2001 Elsevier Science Ltd. All rights reserved.