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.