Efficacy of a Novel Tricyclic Topoisomerase Inhibitor in a Murine Model of Neisseria gonorrhoeae Infection.

There is an urgent need for new antibiotics to treat multidrug-resistant Neisseria gonorrhoeae In this report, the microbiology, in vivo pharmacokinetics, and efficacy of REDX05931, a representative novel tricyclic topoisomerase inhibitor, were evaluated. REDX05931 demonstrated high oral bioavailability in mice and reduced N. gonorrhoeae infection after a single dose in a mouse model of gonorrhea.

Biological profiling of novel tricyclic inhibitors of bacterial DNA gyrase and topoisomerase IV.

Objectives: The objective of this study was to characterize the in vitro and in vivo biological properties of a novel series of small-molecule bacterial type IIA topoisomerase inhibitors.

Methods: Bacterial susceptibility testing was performed by broth microdilution. Resistance frequencies were determined by plating bacteria onto agar containing test compound and enumerating mutants.

The binding of drugs to hepatocytes and its relationship to physicochemical properties.

The binding of 17 drugs to rat hepatocytes has been determined using equilibrium dialysis in combination with metabolic inhibitors and a kinetic model for the binding and dialysis processes. Metabolic inhibitors were used to retard the main routes of metabolism such that the half-life for turnover of the drugs was comparable to or greater than the time scale of the equilibrium dialysis process. Further experiments were carried out to determine the kinetics of diffusion of the compounds across the dialysis membrane and the observed extent of binding to hepatocytes.