The Journal of antimicrobial chemotherapy · 2011
Effectiveness of the local or oral delivery of the novel naphthopterocarpanquinone LQB-118 against cutaneous leishmaniasis.
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da Cunha-Júnior Edézio Ferreira, Pacienza-Lima Wallace, Ribeiro Grazielle Alves, Netto Chaquip Daher, do Canto-Cavalheiro Marilene Marcuzzo, da Silva Alcides José Monteiro, Costa Paulo Roberto Ribeiro, Rossi-Bergmann Bartira, Torres-Santos Eduardo Caio
Аннотация
OBJECTIVES: This paper describes the antileishmanial properties of LQB-118, a new compound designed by molecular hybridization, orally active in Leishmania amazonensis-infected BALB/c mice.
METHODS: In vitro antileishmanial activity was determined in L. amazonensis-infected macrophages. For in vivo studies, LQB-118 was administered intralesionally (15 μg/kg/day, five times a week), intraperitoneally (4.5 mg/kg/day, five times a week) or orally (4.5 mg/kg/day, five times a week) to L. amazonensis-infected BALB/c mice throughout experiments lasting 85 or 105 days. At the end of the experiments, serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine were measured as toxicological parameters.
RESULTS: LQB-118 was active against intracellular amastigotes of L. amazonensis [50% inhibitory concentration (IC(50)) 1.4 μM] and significantly less so against macrophages (IC(50) 18.5 μM). LQB-118 administered intralesionally, intraperitoneally or orally was found to control both lesion and parasite growth in L. amazonensis-infected BALB/c mice, without altering serological markers of toxicity.
CONCLUSIONS: These results demonstrate that the molecular hybridization of a naphthoquinone core to pterocarpan yielded a novel antileishmanial compound that was locally and orally active in an experimental cutaneous leishmaniasis model.
METHODS: In vitro antileishmanial activity was determined in L. amazonensis-infected macrophages. For in vivo studies, LQB-118 was administered intralesionally (15 μg/kg/day, five times a week), intraperitoneally (4.5 mg/kg/day, five times a week) or orally (4.5 mg/kg/day, five times a week) to L. amazonensis-infected BALB/c mice throughout experiments lasting 85 or 105 days. At the end of the experiments, serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine were measured as toxicological parameters.
RESULTS: LQB-118 was active against intracellular amastigotes of L. amazonensis [50% inhibitory concentration (IC(50)) 1.4 μM] and significantly less so against macrophages (IC(50) 18.5 μM). LQB-118 administered intralesionally, intraperitoneally or orally was found to control both lesion and parasite growth in L. amazonensis-infected BALB/c mice, without altering serological markers of toxicity.
CONCLUSIONS: These results demonstrate that the molecular hybridization of a naphthoquinone core to pterocarpan yielded a novel antileishmanial compound that was locally and orally active in an experimental cutaneous leishmaniasis model.
Предметные рубрики MeSH
Administration, OralAdministration, TopicalAlanine TransaminaseAnimalsAntiprotozoal AgentsAspartate AminotransferasesChemical and Drug Induced Liver InjuryCreatinineDisease Models, AnimalInhibitory Concentration 50Leishmania mexicanaLeishmaniasis, CutaneousLiverMiceMice, Inbred BALB CNaphthoquinonesPterocarpansRodent DiseasesSerumTreatment Outcome