Treatment of cutaneous leishmaniasis (CL) is difficult due to the scarce number of drugs able to eliminate completely the intracellular form of the parasite. In the present study, the aim was to evaluate: i) phytochemical properties of extracts from Libidibia ferrea; ii) antileishmanial activity of extracts from L. ferrea against promastigotes and amastigotes of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) guyanensis; iii) the effects of topical treatment using hydrogel containing active extract of L. ferrea on golden hamsters infected with L. (L.) amazonensis. Extracts from leaves, branches and fruits of L. ferrea were obtained with hexane and methanol and were tested by in vitro assays in promastigotes and murine macrophages J774 experimentally infected with amastigotes of Leishmania. Groups of hamsters with CL received topical treatment with a formulation of extract (10%) hydrogels, 50 mg.day ) e baixa citotoxicidade em células de macrófagos J774. Os resultados destacaram que as lesões cutâneas de animais que receberam tratamento com hidrogel + extrato (GelFrMeOH) apresentaram redução significativa (42,78%), menos úlceração e redução da carga parasitária detectada por RT-qPCR, microscopia e análise em cultura e alterações histopatológicas, como menor infiltrado inflamatório após 40 dias de tratamento. A análise química demonstrou que FrMeOH contém altos níveis de compostos fenólicos. Os resultados apontam para uma possível terapia alternativa para CL utilizando fitoterápicos. PALAVRAS-CHAVE: leishmaniose cutânea, formulações tópicas, produtos naturais, tratamento experimental

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In the research for the development of new drugs for the therapy of American tegumentary leishmaniasis, copper has been studied for its antileishmania activity. This study aims to report the activity of three copper(I) complexes on parasites of the species L. amazonensis and L. guyanensis. The metal complexes were tested according to in vitro antileishmanial assays, against promastigote and amastigote forms of the most prevalent species in the state of Amazonas, Brazil. Cytotoxicity of the complexes was evaluated in murine macrophage-like cell line (MJ774). The results of the in vitro assays indicated that, among the copper complexes tested, the homoleptic phosphine complex [Cu(thp)4][PF6](thp=tris-hydroxymethylphosphine) presented promising activity against the evolutionary forms of L. amazonensis, and obtained a IC50 of  26.45 and 24.61 µM in a period of 48 and 72 h, respectively. The results for copper complex at concentration 160 µM in amastigote forms showed a decrease in the infection index (32% of infected cells) and, in the cytotoxicity assay with MJ774, 52.43% of cell viability was observed. The results showed that the complex [Cu(thp)4][PF6] presented significant biological activity, indicating a need for future in vivo studies.

Current treatment of cutaneous leishmaniasis (CL) relies mainly on pentavalent antimonials salts and second-line drugs include pentamidine and amphotericin B, but these therapies have side effects and require parenteral administration. The aim of this work was to evaluate the topical formulations containing pentamidine isethionate (PI) in the experimental treatment of cutaneous leishmaniasis (CL). Golden hamsters (Mesocricetus auratus) were infected in the nose with Leishmania (Leishmania) amazonensis. Six treatment groups received different topical treatments of anhydrous or hydrating emulsions, for a maximum of 10 days, with an application of 50 mg day -1. After treatment tissue samples of lesions were evaluated by histology, transmission electron microscopy and biopsy cultivation. Compared with untreated group, topical treatment with hydrating emulsion with 10% PI and usnic acid (ACE5AU) showed significantly decrease in volume lesion (P= 0.028) on 20 th day after the end of the treatment with reduction of 27.37%. Topical treatment with anhydrous emulsion with 10% PI and usnic acid (ACPU) reduces parasite burden in Golden hamsters. This study demonstrated the potential of topical treatment to reduce the number of parasites that could be combined with others drugs and to have a faster and more effective treatment of cutaneous leishmaniasis.

A malária ao longo dos anos tem acometido pessoas que residam ou visitam áreas de transmissão no Amazonas. Em Manaus, capital do estado, desde a implantação da Zona Franca de Manaus tem sido um atrativo para as populações inclusive de outras regiões do país, em busca de melhores condições de vida, se instalam nas áreas que são desmatadas pelo processo de invasões. A malária é um agravo preocupante na saúde publica, que pela sua morbidade causa impacto negativo sobre a economia regional pelo elevado tempo que incapacita aos acometidos pela doença, deixando-os fora do mercado de trabalho. O estudo busca descrever o registro dos casos de maláriae seus aspectos epidemiológicos, na cidade de Manaus, de 2008 a 2017.

First isolated from the tropical plant Oschrosia elliptica, indole alkaloid ellipticine provoked huge interest since it demonstrated antitumor activity was demonstrated along with limited toxic side effects and a complete lack of hematological toxicity. In this work, a five-step Cranwell and Saxton synthesis was used for obtaining ellipticine (Ell). Ellipticine hydrochloride salt (Ell×HCl) was also synthesized. Detailed in vitro studies of anticancer, antimalarial, and leishmanicidal activities were performed. Antiproliferation assay using DU145 cancer cell line treated with Ell showed a consistent reduction in cell proliferation and cell viability when treated with 5 μmol Ell. Anti-proliferation activity was more pronounced for the Ell×HCl solutions. Both the Ell and Ell×HCl revealed moderate activity in vitro against Leishmania amazonensis promastigotes, which is related to insufficient solubility of the drugs. IC50 values of Ell and Ell×HCl were determined in vitro against multidrug resistant Plasmodium falciparum strain K1. The Ell×HCl was shown to be almost three times more potent than the Ell in DMSO. Upon dilution with water, Ell solubility and activity drops down, while the activity and solubility of Ell×HCl is enhanced up to 10 times in 50:50 aqueous DMSO solutions

ResumoA Leishmaniose é considerada uma doença negligenciada. Nos últimos anos estudos tem demonstrado que várias plantas possuem atividade contra esses patógenos, servindo de base para a formulação de fitoterápicos ou como alvo para a obtenção de princípios ativos contra a doença. Esta pesquisa teve como objetivo avaliar a atividade biológica in vitro antileishmania dos extratos hexânicos e metanólicos das flores e folhas de Tanacetum vulgare contra Leishmania amazonensis e Leishmania guyanensis. Foi realizada a extração das flores e folhas do material vegetal a partir dos solventes hexânico e metanólico. The results showed that the extract metanolic of the flower showed activity against L. amazonensis (IC50 = 31.5 μg mL -1 ) and L. guyanensis (IC50 < 100 μg mL -1 ) in 72 h of incubation. Therefore, it is verified that the methanolic extract of the T. vulgare flower performed better in relation to antileishmania activity, allowing the possibility of future studies to determine its therapeutic efficacy.

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