title: In vitro and in vivo antileishmanial efficacy of a new nitrilquinoline against Leishmania donovani.
abstract: The in vitro activity of a new analogue of 2-alkenylquinoline (2-nitrilquinoline or NQ) against Leishmania donovani was compared to oral reference drug miltefosine (HePC). IC(50) of NQ was found at 38.6 microM against promastigotes and 2.4 microM against intramacrophage amastigotes. In vivo evaluation in the L. donovani Balb/c mice model indicated that oral treatments at 12.5 and 25 mg/kg for 10 consecutive days significantly reduced the parasite burden in the liver by 68.9 and 68.5%, respectively. This activity was similar to those of HePC at 7.5 mg/kg for 10 days which reduced the parasite burden in liver by 72.5%. The present study shows the positive contribution of a nitril substitute being added into the alkenyl chain branched at the 2-position of the quinoline ring to the antileishmanial activity. In addition, any apparent toxicological disorder was observed during the experiments.
authors.affiliation: Department of Tropical Medicine, Casilla de Correo 2511, Instituto de Investigaciones en Ciencias de la Salud Asunción, Universidad Nacional de Asuncion, Asuncion, Paraguay.
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.forename: J
authors.initials: J
authors.lastname: Desrivot
authors.forename: C
authors.initials: C
authors.lastname: Bories
authors.forename: X
authors.initials: X
authors.lastname: Franck
authors.forename: B
authors.initials: B
authors.lastname: Figadère
authors.forename: R
authors.initials: R
authors.lastname: Hocquemiller
authors.forename: A
authors.initials: A
authors.lastname: Fournet
authors.forename: P M
authors.initials: PM
authors.lastname: Loiseau
mesh_terms: D000181:Acrylonitrile / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: C521193:2-nitrilquinoline; D000981:Antiprotozoal Agents; D011804:Quinolines; D010767:Phosphorylcholine; C039128:miltefosine; D000181:Acrylonitrile