Author | Cunha Junior, Edézio Ferreira | |
Author | Martins, Thiago Martino | |
Author | Cavalheiro, Marilene Marcuzzo Canto | |
Author | Marques, Paulo Roberto | |
Author | Portari, Elyzabeth Avvad | |
Author | Coelho, Marsen Garcia Pinto | |
Author | Netto, Chaquip Daher | |
Author | Costa, Paulo Roberto Ribeiro | |
Author | Sabino, Katia Costa de Carvalho | |
Author | Santos, Eduardo Caio Torres | |
Access date | 2017-02-09T14:45:46Z | |
Available date | 2017-02-09T14:45:46Z | |
Document date | 2016 | |
Citation | CUNHA JUNIOR, Edézio Ferreira; et al. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis. Antimicrobial Agents and Chemotherapy, v.60, n.6, p.3794-3801, June 2016. | pt_BR |
ISSN | 0066-4804 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/17770 | |
Language | eng | pt_BR |
Publisher | American Society for Microbiology | pt_BR |
Rights | open access | |
Subject in Portuguese | Leishmaniose visceral | pt_BR |
Subject in Portuguese | Toxicidade subaguda | pt_BR |
Subject in Portuguese | Eficácia Terapêutica | pt_BR |
Subject in Portuguese | Pterocarpanquinona | pt_BR |
Title | Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis | pt_BR |
Type | Article | |
DOI | 10.1128/AAC.01787-15 | |
Abstract | Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Universidade do Estado do Rio de Janeiro. Laboratório Imunol. Aplicada e Bioq. de Proteínas e Prod. Naturais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Universidade do Estado do Rio de Janeiro. Laboratório Imunol. Aplicada e Bioq. de Proteínas e Prod. Naturais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade do Estado do Rio de Janeiro. Departamento de Patologia e Laboratórios. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade do Estado do Rio de Janeiro. Laboratório Imunol. Aplicada e Bioq. de Proteínas e Prod. Naturais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Laboratório de Química. Macaé, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Pesquisas de Produtos Naturais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade do Estado do Rio de Janeiro. Laboratório Imunol. Aplicada e Bioq. de Proteínas e Prod. Naturais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil. | pt_BR |
Subject | Visceral leishmaniasis | pt_BR |
Subject | Subacute Toxicity | pt_BR |
Subject | Therapeutic efficacy | pt_BR |
Subject | LQB-118 | pt_BR |
e-ISSN | 1098-6596 | |