title: Effectiveness of the local or oral delivery of the novel naphthopterocarpanquinone LQB-118 against cutaneous leishmaniasis.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Edézio Ferreira
authors.initials: EF
authors.lastname: da Cunha-Júnior
authors.forename: Wallace
authors.initials: W
authors.lastname: Pacienza-Lima
authors.forename: Grazielle Alves
authors.initials: GA
authors.lastname: Ribeiro
authors.forename: Chaquip Daher
authors.initials: CD
authors.lastname: Netto
authors.forename: Marilene Marcuzzo
authors.initials: MM
authors.lastname: do Canto-Cavalheiro
authors.forename: Alcides José Monteiro
authors.initials: AJ
authors.lastname: da Silva
authors.forename: Paulo Roberto Ribeiro
authors.initials: PR
authors.lastname: Costa
authors.forename: Bartira
authors.initials: B
authors.lastname: Rossi-Bergmann
authors.forename: Eduardo Caio
authors.initials: EC
authors.lastname: Torres-Santos
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008099:Liver / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D036343:Pterocarpans / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D012376:Rodent Diseases / Q000188:drug therapy / Q000469:parasitology; D044967:Serum / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; C569361:LQB 118; D009285:Naphthoquinones; D036343:Pterocarpans; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase