In vivo efficacy of oral and intralesional administration of 2-substituted quinolines in experimental treatment of new world cutaneous leishmaniasis caused by Leishmania amazonensis

Abstract

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.

Efficacy of the intralesional treatment with Chenopodium ambrosioides in the murine infection by Leishmania amazonensis

“…The C3H/HePas mice were chosen because they are susceptible to the infection by the Leishmania amazonensis promastigotes and develop chronic cutaneous lesions when infected in the footpad (Vanloubbeeck and Jones, 2004). The protocol of treatment was similar to that described by Fournet et al (1996) which used the oral and intralesional treatments after the 4th week of infection, when the lesion is already established. It is important to emphasize that this protocol permits the reproduction of the methods of treatment used by the population in the endemic areas (França et al, 1996).…”

“…The protocol used to treat the animals was adapted from Fournet et al (1996). The intralesional treatment was initiated on the 23rd day post-infection (p.i.).…”

Determination of the human cytochrome P450s involved in the metabolism of 2n-propylquinoline

“…First choice drugs are pentavalent antimonials such as sodium stilbogluconate and meglumine antimonate. In spite of their activity in kala-azar, diamidines (pentamidine) and amphotercin B are second-line drugs because of their toxicity (Fournet et al 1996(Fournet et al ). xenobiotica, 2003 In Bolivia, the Instituto Boliviano de Biologia de Altura and the French Institute of Scientific Research for Development in Cooperation (ORSTOM) have developed alternative compounds for the treatment of leishmaniasis.…”

Progresses in the Field of Drug Design to Combat Tropical Protozoan Parasitic Diseases

“…2-Alkyl and 2-arylquinolines proved to have interesting pharmacological properties such as against Leishmania spp. [262], Plasmodium [263], Trypanosoma spp. [264] and also were found to inhibit the human immunodeficiency virus of type-1 targeting (HIV-1) integrase [265,266].…”