AAC Accepts, published online ahead of print on 2 November 2009

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Antimicrob. Agents Chemother. doi:10.1128/AAC.01001-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

In-vitro and in-vivo activity of 1-hydroxy-2-alkyl-4(1H)quinolone derivatives against Toxoplasma gondii

Lara Liv Bajohr, Ling Ma, Christian Platte, Oliver Liesenfeld, Lutz F. Tietze, Uwe Groß, and Wolfgang Bohne^*

Institut für Mikrobiologie und Hygiene, Charité Universtätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 27, 12203 Berlin, Germany; Institut für Organische und Biomolekulare Chemie, Universität Göttingen, Tammannstr. 2, D-37077 Göttingen, Germany; Institut für Medizinische Mikrobiologie, Universitätsmedizin Göttingen, Kreuzbergring 57, D-37075 Göttingen, Germany

^* To whom correspondence should be addressed. Email: wbohne{at}gwdg.de.

1-hydroxy-2-dodecyl-4(1)quinolone (HDQ) was recently identified as a Toxoplasma gondii inhibitor. We describe here two novel 1-hydroxyquinolones, which displayed a 10- and 5-fold lower IC₅₀ than HDQ. In a mouse model of acute toxoplasmosis these two compounds and HDQ reduced the percentage of infected peritoneal cells and decreased the parasite load in lung and liver. Compound B showed a tendency towards lower parasite loads in brains in a mouse model of toxoplasmic encephalitis.