High-performance liquid chromatography evaluation of lipophilicity and QSRR modeling of a series of dual DNA gyrase and topoisomerase IV inhibitors

Abstract Bacterial DNA gyrase and topoisomerase IV control the topological state of during replication represent important antibacterial drug targets. To be successful as candidates, newly synthesized compounds must possess optimal lipophilicity, which enables efficient delivery to site action. In this study, retention behavior twenty-three previously dual inhibitors was tested in RP-HPLC system, consisting C8 column acetonitrile/phosphate buffer (pH 5.5 pH 7.4) mobile phase. logD calculated at both values best correlation with obtained for parameter φ0 , indicating that system could used an alternative shake-flask determination lipophilicity. Subsequent QSRR analysis revealed intrinsic lipophilicity ( logP ) molecular weight bcutm13 have a positive, while solubility bcutp3 has negative influence on parameter.