The activity of 2-substituted quinoline alkaloids in BALB/c mice infected with Leishmania donovani.
Potent antileishmanial activity has recently been described in vivo when certain 2-substituted quinoline alkaloids are administered to mice with cutaneous leishmaniasis. We now report the antileishmanial activity of four 2-substituted quinoline alkaloids, namely chimanine D or 2-(1',2'-trans-epoxypropyl) quinoline (I), 2-n-propylquinoline (II), 2-styrylquinoline (III) and 2-(2'-hydroxypropyl) quinoline (IV), for experimental treatment of visceral leishmaniasis in infected BALB/c mice. Subcutaneous treatment with chimanine D for 10 days at 0.54 mmol/kg per day resulted in 86.6% parasite suppression in the liver. Oral administration of 0.54 mmol/kg of 2-n-propylquinoline once daily for 5 or 10 days to L. donovani-infected mice suppressed parasite burdens in liver by 87.8 and 99.9%, respectively. Cutaneous administration of meglumine antimonate for 10 days resulted in 97.4% parasite suppression in the liver. This study is, to our knowledge, the first to demonstrate the activity of 2-substituted quinoline alkaloids in experimental treatment of visceral leishmaniasis. Further biological and chemical studies of these products might yet prove helpful for the development of new antileishmanial drugs.
Fournet
A
A
ORSTOM (Institut Français de Recherche Scientifique pour le Développement en Coopération), Département Santé, Paris, France.
Gantier
J C
JC
Gautheret
A
A
Leysalles
L
L
Munos
M H
MH
Mayrargue
J
J
Moskowitz
H
H
Cavé
A
A
Hocquemiller
R
R
D000470:Alkaloids / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D006224:Cricetinae; D005260:Female; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000890:Anti-Infective Agents; D011804:Quinolines