Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Nakayama, H. et al.

Efficacy of orally administered 2-substituted quinolines in experimental murine cutaneous and visceral leishmaniases.

We report in this study the in vivo efficacy of nine 2-substituted quinolines on the Leishmania amazonensis cutaneous infection murine model and on the Leishmania infantum and Leishmania donovani visceral infection murine models. In the case of the L. amazonensis model, quinolines were administered orally at 25 mg/kg twice daily for 15 days. Quinolines 1, 2, 3, and 7 reduced by 80 to 90% the parasite burdens in the lesion, whereas N-methylglucamine antimoniate (Glucantime), administered by subcutaneous injections at 100 mg [28 mg Sb(V)] per kg of body weight daily, reduced the parasite burdens by 98%. In visceral leishmaniasis due to L. infantum, mice treated orally at 25 mg/kg daily for 10 days with quinolines 1, 4, 5, and 6 showed a significant reduction of parasite burdens in the liver and spleen. These quinolines were significantly more effective than meglumine antimoniate to reduce the parasite burden in both the liver and spleen. Also, the oral in vivo activity of three quinolines (quinolines 4, 5, and 2-n-propylquinoline) were determined against L. donovani (LV 9) at 12.5 and 25 mg/kg for 10 days. Their activity was compared with that of miltefosine at 7.5 mg/kg. Miltefosine, 2-n-propylquinoline, and quinoline 5 at 12.5 mg/kg significantly reduced the parasite burdens in the liver by 72, 66, and 61%, respectively. From the present study, quinoline 5 is the most promising compound against both cutaneous and visceral leishmaniasis. The double antileishmanial and antiviral activities of these compounds suggest that this series could be a potential treatment for coinfection of Leishmania-human immunodeficiency virus.[1]

References

Efficacy of orally administered 2-substituted quinolines in experimental murine cutaneous and visceral leishmaniases. Nakayama, H., Loiseau, P.M., Bories, C., Torres de Ortiz, S., Schinini, A., Serna, E., Rojas de Arias, A., Fakhfakh, M.A., Franck, X., Figadère, B., Hocquemiller, R., Fournet, A. Antimicrob. Agents Chemother. (2005) [Pubmed]

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