Development of pharmacophore model for S. Aureus DNA-gyrase inhibitors

Pharmacophore mapping studies were undertaken for a series of molecules belonging to indazole, pyrazole and their congeners as inhibitors of S. Aureus DNA gyrase. A four point pharmacophore with two aromatic rings (R), one lipophilic/hydrophobic group (H) and one positive ionic feature (P) as pharmacophoric features was developed. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with correlation coefficient of r2 = 0.681 for training set molecules. The model so generated showed good predictive power with correlation coefficient for an external test set of fifteen molecules. The geometry and features of the pharmacophore will be useful for ligand based design of potential DNA gyrase inhibitors.