Selection of the most promising 2-substituted quinoline as antileishmanial candidate for clinical trials.
The antileishmanial evaluation of more than one hundred 2-substituted quinolines led us to identify three compounds for further studies: compound 1 (2-n-propylquinoline), compound 2 (2-(2methoxyethenyl)quinoline) and compound 3 (2-(2-hydroxyprop-2-enyl)quinoline). The final selection of a potential drug candidate was mainly based on chemical stability and acute oral toxicity as discriminating criteria. The most stable compound in various conditions was 2-n-propylquinoline (compound 1). Only reversible toxicity signs were observed for compound 1 at 1000 mg/kg after a treatment by oral route at a single dose and no sign was detected at 100 mg/kg. Interestingly, 2-substituted quinolines were active on a Leishmania donovani line, resistant to sitamaquine, a 8-aminoquinoline, suggesting that 2-substituted quinolines and 8-aminoquinoline probably affect a different target in L. donovani.
Laboratoire de Pharmacognosie Groupe de et Chimiothérapie Antiparasitaire UMR 8076 CNRS, Faculté de Pharmacie, Université Paris-Sud, Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France.
Nashira Campos
NC
Vieira
Christine
C
Herrenknecht
Joel
J
Vacus
Alain
A
Fournet
Christian
C
Bories
Bruno
B
Figadère
Laila Salmen
LS
Espindola
Philippe M
PM
Loiseau
D000818:Animals; D004351:Drug Resistance; D004355:Drug Stability; D007893:Leishmania donovani / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D011804:Quinolines / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D023382:Toxicity Tests, Acute; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology
C116019:2-propylquinoline; D011804:Quinolines; D014344:Trypanocidal Agents