Antiprotozoal activity of the cyclopalladated complexes against leishmania amazonensis and trypanosoma cruzi

The present study describes the antiprotozoal activities of four cyclopalladated compounds, [Pd(dmba)(μ-Cl)]2, [Pd(dmba)(NCO)(isn)], [Pd(dmba)(N3)(isn)] and [Pd(dmba)(μ-NCO)]2, (dmba: N,N'-dimethylbenzylamine and isn: isonicotinamide), against the diseases leishmaniasis (Leishmania amazonensis and Leishmania infantum), Chagas disease (Trypanosoma cruzi) and human African trypanosomiasis (Trypanosoma brucei). [Pd(dmba)(μ-NCO)]2 exhibited good leishmanicidal and trypanocidal activities against L. amazonensis and T. cruzi intracellular amastigote forms, with a 50% inhibitory concentration (IC50) value of less than 9 µM and selectivity indexes of 14.47 and 28.42, respectively. Stability essays were conducted in phosphate buffer saline (PBS) pH 7.0 and showed that [Pd(dmba)(μ-NCO)]2 is the most stable molecule. These findings indicate that this compound presented higher selectivity for these parasites than the other tested compounds. The data presented here suggest that this compound should be considered in the development of new and more potent drugs for the treatment of leishmaniasis and Chagas disease27610321039COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informação201308248-

Leishmanicidal activity of Brosimum glaziovii (Moraceae) and chemical composition of the bioactive fractions by using high-resolution gas chromatography and GC-MS

As part of our ongoing SisBiota CNPq/FAPESP and Biota-FAPESP bioprospecting programs, this paper deals with the leishmanicidal properties of Brosimum glaziovii (Moraceae), and used gas chromatography analysis to determine the chemical composition of these fractions. The extracts and fractions from the leaves and branches of B. glaziovii were screened against Leishmania amazonensis. The hexane fractions from the leaves and branches displayed the highest leishmanicidal activities, with IC50 = 3.6 and 39.1 µg mL-1. Using gas chromatography analysis it was possible to identify the sterols campesterol, stigmasterol, and β-sitosterol, as well as the triterpenes α-amyrin, β-amyrin, β-amyrin acetate, and lupenone, and other nonpolar components, mainly fatty acids and their derivatives. This is the first report on the leishmanicidal activity and the chemical composition of B. Glaziovii.Dando continuidade às pesquisas de bioprospecção dos programas SisBiota CNPq/FAPESP e Biota-FAPESP, o presente artigo descreve os resultados de atividade leishmanicida e determinação da composição química das frações ativas de Brosimum glaziovii (Moraceae), por meio da cromatografia gasosa. Os extratos e frações das folhas e galhos foram testados in vitro em cepas de Leishmania amazonensis. As frações hexânicas das folhas e galhos apresentaram atividades potente e moderada, respectivamente (IC50 = 3,6 e 39,1 µg mL-1). Por meio das análises de cromatografia gasosa foi possível identificar os esteróis: campesterol, β-sitosterol e estigmasterol e os triterpenos: α-amirina, β-amirina, acetato de β-amirina, e lupenona, além de outros constituintes apolares principalmente ácidos graxos e seus derivados. Este é o primeiro trabalho descrito sobre a atividade leishmanicida e composição química desta espécie.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

The 2',4'-dihydroxychalcone could be explored to develop new inhibitors against the glycerol-3-phosphate dehydrogenase from Leishmania species

The enzyme glycerol-3-phosphate dehydrogenase (G3PDH) from Leishmania species is considered as an attractive target to design new antileishmanial drugs and a previous in silico study reported on the importance of chalcones to achieve its inhibition. Here, we report the identification of a synthetic chalcone in our in vitro assays with promastigote cells from Leishmania amazonensis, its biological activity in animal models, and docking followed by molecular dynamics simulation to investigate the molecular interactions and structural patterns that are crucial to achieve the inhibition complex between this compound and G3PDH. A molecular fragment of this natural product derivative can provide new inhibitors with increased potency and selectivity.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP