Avaliação da atividade leishmanicida in vitro de adutos do lapachol sobre Leishmania amazonensis

Abstract

The Leishmaniasis caused by different species of Leishmania are infectious diseases that have great relevance for public health. The therapy currently used to treat those diseases is based on pentavalent antimony. However these drugs have presented several side effects. Naphthoquinones are compounds that can be found in several plants and that have been studied very much because of their high variety of biological activities demonstrated in vitro and in vivo. Among those naphthoquinones, lapachol and its derivatives have been presenting leishmanicidal, antitumor, tripanosomatida and other actions. This study is aimed at evaluating the in vitro leishmanicidal action of five synthetic naphthoquinones derived from lapachol in vitro on promastigotes of Leishmania amazonensis as well as evaluating its cytotoxic action on J774 lineage murine macrophages and on mice’s peritoneal macrophages using two different quantitative methods: direct counting in a Neubawer chamber and cytotoxicity test by counting ATP molecules by luminescence. Ultrastructured modifications of Leishmania amazonensis promastigotes treated using the naphthoquinones testadas were evaluated through Transmission Eletronic Microscopie. The five synthetic naphthoquinones have presented leishmanicidal action, although the naphthoquinone 31 (C34H35N2O2), which showed the highest activity (IC50 = 23.37 mg / ml) but showed high toxicity for both peritoneal macrophacrophages getting a better selectivity index. Treatment with quinones induced morphological changes consistent with loss of viability and cell death, such as a general disruption of cell swelling and disruption of mitochondrial structure and appearance of vacuoles with membrane profiles. This study concluded that the quantitative method cytotoxicity luminescence was the most sensitive, and strengthen the greater resistance of peritoneal macrophages in front substances tests compared to the J774 cell line. We also conclude, the need for further studies with these synthetic naphthoquinones, due to the same potential as antileishmanial drugs because although the cytotoxicity in macrophages, the naphthoquinones showed significant leishmanicidal action, enabling future studies in amastigotes in order to obtain a better index selectivity.