Atividade da naftoquinona sintética LQB-166 em Leishmania (Viannia) braziliensis

• Autor(a) principal: Meira, Rafaella de Miranda Villarim
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/14444
• topic: Leishmaniasis; Treatment; Naphthoquinone; Leishmania (Viannia) braziliensis; Leishmaniose; Tratamento; Naftoquinona; Leishmania (Viannia) braziliensis; Leishmaniose Tratamento; Naftoquinona; Leishmania brasiliensis; CNPQ::CIENCIAS BIOLOGICAS::PARASITOLOGIA::PROTOZOOLOGIA DE PARASITOS

Leishmaniasis are neglected diseases with different clinical outcomes and are caused by protozoa of the genus Leishmania. In Brazil, the main agent of cutaneous and mucosal leishmaniasis is Leishmania (Viannia) braziliensis. The current therapeutic arsenals available for these diseases are toxic, expensive and parasite resistance is a growing problem. Given this scenario it is necessary to expand the alternatives for treatment of leishmaniasis. Naphthoquinones are bioactive molecules with antitumor and antiprotozoal activities. The aim of this study was to evaluate the effect of the naphthoquinone LQB-166 (2-hydroxy-3-phenyl-1,4-naphthoquinone) on L. (V.) braziliensis in vitro and in experimental models of infection. LQB-166 showed activity in vitro on promastigotes (IC50 = 598 ± 70 μM) and intracellular amastigotes (IC50 = 193 ± 19 μM) of L. (V.) braziliensis with low toxicity for the macrophages (LC50 = 3200µM). The macrophages infected with L. (V.) braziliensis and treated with LQB-166 presented a significative reduction on the intracellular amastigotes number. The treatment of infected macrophages with LQB-166 did not induce the nitric oxide production, but significantly increased the production of pro-inflammatory cytokines (IL-6, TNF, MCP-1) and anti-inflammatory (IL-10). In vivo LQB-166 was capable of controlling the lesion size and significantly decrease the parasite load (p<0,001) on BALB/c mice. On golden hamsters treated with LQB-166 the reduction of the lesion was small, but the parasite load in the infected footpad and draining lymph node was significantly reduced (p<0,001). These data show that LQB-166 has activity against L. (V.) braziliensis in vitro and in vivo, therefore it is a promising molecule to continued preclinical studies.