In vivo efficacy of oral and intralesional administration of 2-substituted quinolines in experimental treatment of new world cutaneous leishmaniasis caused by Leishmania amazonensis.
The antileishmanial efficacies of 2-n-propylquinoline, chimanines B and D, 2-n-pentylquinoline, 2-phenylquinoline, 2-(3,4-methylenedioxyphenylethyl) quinoline, and two total alkaloidal extracts of Galipea longiflora were evaluated in BALB/c mice infected with Leishmania amazonensis or Leishmania venezuelensis. Animals were treated for 4 to 6 weeks postinfection with a quinoline by the oral route at 50 mg/kg of body weight twice daily for 15 days or by five intralesional injections at intervals of 4 days with a quinoline at 50 mg/kg of body weight. The reference drug, N-methylglucamine antimonate (Glucantime), was administered by subcutaneous or intralesional injection (regimens of 14, 28, or 56 mg of pentavalent antimony [Sbv] per kg of body weight daily). Twice-daily oral treatment with chimanine B at 50 mg/kg resulted in a decrease in lesion weight by 70% (P < 0.001) and a decrease in the parasite loads by 95% (P < 0.001). Five injections of chimanine B at intervals of 4 days reduced the lesion weight by 74% and the parasite loads in the lesion by 90% compared with the values for the group of untreated mice. Subcutaneous administration of N-methylglucamine antimonate at 28 mg of Sbv kg per day for 15 days reduced the parasite burden by 95% (P < 0.001), and five intralesional injections at the same concentration reduced the parasite burden by 96% (P < 0.001). Other 2-substituted quinolines, 2-n-propylquinoline administered by the oral and intralesional routes, 2-phenylquinoline administered by the oral route, 2-n-pentylquinoline administered by intralesional injection, and two total alkaloidal extracts of G. longiflora administered by the oral route, had intermediate effects. These findings suggest that chimanine B may be chosen as a lead molecule in the development of oral therapy against leishmaniasis.
Fournet
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A
ORSTOM, Institut Français de Recherche Scientifique pour le Développement en Coopération, Asunción, Paraguay. fournet@ui131.una.py
Ferreira
M E
ME
Rojas De Arias
A
A
Torres De Ortiz
S
S
Fuentes
S
S
Nakayama
H
H
Schinini
A
A
Hocquemiller
R
R
D042462:4-Quinolones; D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D007279:Injections, Subcutaneous; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D010936:Plant Extracts / Q000627:therapeutic use; D010946:Plants, Medicinal
D042462:4-Quinolones; D000890:Anti-Infective Agents; D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D010936:Plant Extracts; D008536:Meglumine; D000077485:Meglumine Antimoniate