title: Efficacy of orally administered 2-substituted quinolines in experimental murine cutaneous and visceral leishmaniases.
abstract: 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.
authors.affiliation: Department of Tropical Medicine, Casilla de Correo, Instituto de Investigaciones en Ciencias de la Salud Asunción, Universidad Nacional de Asuncion, Paraguay.
authors.forename: Hector
authors.initials: H
authors.lastname: Nakayama
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: Christian
authors.initials: C
authors.lastname: Bories
authors.forename: Susana
authors.initials: S
authors.lastname: Torres de Ortiz
authors.forename: Alicia
authors.initials: A
authors.lastname: Schinini
authors.forename: Elsa
authors.initials: E
authors.lastname: Serna
authors.forename: Antonieta
authors.initials: A
authors.lastname: Rojas de Arias
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Fakhfakh
authors.forename: Xavier
authors.initials: X
authors.lastname: Franck
authors.forename: Bruno
authors.initials: B
authors.lastname: Figadère
authors.forename: Reynald
authors.initials: R
authors.lastname: Hocquemiller
authors.forename: Alain
authors.initials: A
authors.lastname: Fournet
mesh_terms: D000284:Administration, Oral; D032761:Animal Experimentation; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007891:Leishmania / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011804:Quinolines / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D000981:Antiprotozoal Agents; D011804:Quinolines