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.
ORSTOM (Institut Français de Recherche Scientifique pour le Développement en Coopération), Département Santé, Paris, France.
A
A
Fournet
J C
JC
Gantier
A
A
Gautheret
L
L
Leysalles
M H
MH
Munos
J
J
Mayrargue
H
H
Moskowitz
A
A
Cavé
R
R
Hocquemiller
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