title: Antileishmanial 2-substituted quinolines: in vitro behaviour towards biological components.
abstract: Quinolines substituted on their carbon 2 have in vivo antileishmanial activity but some of them could not be detected in plasma when assayed for pharmacokinetic studies, suggesting a sequestration of the drugs by components of the blood compartment. The present study, performed on three quinolines (1, 2 and 3), showed strong affinity for two of them (2 and 3) with red blood cells (RBCs), whereas quinoline 1 did not react with them. This process was saturable, temperature dependant and positively correlated with the in vitro antileishmanial activity of the quinolines. In addition, a rapid and spontaneous reaction with thiol groups was demonstrated for unsaturated quinolines 2 and 3. The reactivity with RBCs could be part of the compounds targeting to the parasite. These results illustrate that derivatives of the quinoline series with similar antileishmanial in vivo activity have different behaviour in the blood compartment.
authors: Laboratoire de Pharmacognosie et Chimiothérapie Antiparasitaire, Centre d'Etudes Pharmaceutiques, BioCIS UMR 8076, Université Paris-Sud 11, 5 rue J-B Clément, 92290 Châtenay-Malabry, France.
authors: Julie
authors: J
authors: Desrivot
authors: Christine
authors: C
authors: Herrenknecht
authors: Gilles
authors: G
authors: Ponchel
authors: Najla
authors: N
authors: Garbi
authors: Eric
authors: E
authors: Prina
authors: Alain
authors: A
authors: Fournet
authors: Christian
authors: C
authors: Bories
authors: Bruno
authors: B
authors: Figadère
authors: Reynald
authors: R
authors: Hocquemiller
authors: Philippe M
authors: PM
authors: Loiseau
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D007894:Leishmania mexicana / Q000187:drug effects*; D008297:Male; D051379:Mice; D021261:Parasitic Sensitivity Tests; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D052616:Solid Phase Extraction; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D000981:Antiprotozoal Agents; D011804:Quinolines