A novel and potent (Ki = 0.01 nM) Staphylococcus aureus enoyl-ACP reductase (saFabI) inhibitor (PT119), identified from a saFabI inhibitor library, showing favorable interactions with the target enzyme and a long residence time (750 min), was radiolabeled with carbon-11 to evaluate its biodistribution and pharmacokinetics in both healthy and S. aureus infected mice using positron emission tomography (PET). The biodistribution of [11C]PT119 and/or its labeled metabolites does not differ significantly between the healthy group and the infected group. Furthermore, we evaluated the in vivo antibacterial efficacy of PT119. The drug showed promising efficacy in two different S. aureus infection models: it decreased 3 Log CFU in the thigh muscle infection model and increased the survival rate from 0% - 50% in the systemic infection model. This approach is important to determine biodistribution and pharmacokinetics of novel drugs as well as to screen tracers for bacterial infection imaging.

Radiosynthesis and biological evaluation of a novel Enoyl-ACP reductase inhibitor for <i>Staphylococcus aureus</i>

248th National Meeting (2014)

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Radiosynthesis and biological evaluation of a novel Enoyl-ACP reductase inhibitor for Staphylococcus aureus