naphthoquinones and Rodent-Diseases

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.. 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.. 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.. 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.

Topics: Administration, Oral; Administration, Topical; Alanine Transaminase; Animals; Antiprotozoal Agents; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Creatinine; Disease Models, Animal; Inhibitory Concentration 50; Leishmania mexicana; Leishmaniasis, Cutaneous; Liver; Mice; Mice, Inbred BALB C; Naphthoquinones; Pterocarpans; Rodent Diseases; Serum; Treatment Outcome