Os únicos fármacos aprovados para o tratamento da doença de Chagas, nifurtimox e benznidazol, apresentam efeitos colaterais e eficácia limitada na fase crônica da doença, destacando a necessidade de novos fármacos. Entre os diferentes alvos moleculares de fármacos identificados no parasita, uma trans-sialidase de Trypanosoma cruzi (TcTS) tem sido considerada essencial para o reconhecimento e invasão nas células do hospedeiro. Desta forma, o trabalho descreve a síntese eficiente e a avaliação biológica (inibição de TcTS e atividade antitripanossoma) de alguns triazol-arilsulfonamidas contendo galactose pela reação de 1,3-dipolar de cicloadição azida-alcino Cu(I) (CuAAC) em micro-ondas, usando como precursores os derivados de azido benzenossulfonamidas e alcino derivado de galactose. A maioria dos compostos testados contra TcTS mostrou inibição moderada a fraca (40%-15%), com exceção de um dos compostos (81%). Quanto ao ensaio de atividade antitripanossoma, alguns compostos [(IC50 70,9 µM) e (IC50 44,0 µM)] apresentaram atividades mais significativas, embora não tenham sido tão ativos como benznidazol (IC50 1,4 µM). Adicionalmente, a avaliação da citotoxicidade mostrou que todos os compostos não foram citotóxicos. Neste trabalho preliminar, alguns compostos foram considerados protótipos para posterior otimização.

The only drugs approved for the treatment of Chagas disease, nifurtimox and benznidazole, present toxic side effects and limited efficacy in the chronic stage of the disease, which highlight the need for new drugs. Amongst the different molecular drug targets discovered in the parasite, Trypanosoma cruzi trans-sialidase (TcTS) has been considered crucial in the recognition and invasion of host cells. Hence, we report the efficient synthesis and biological evaluation (TcTS inhibition and antitrypanosomal activities) of some galactose-containing triazol-arylsulfonamides via microwave-assisted Cu(I) 1,3-dipolar azide-alkyne cycloaddition (CuAAC) based on azide benzenesulfonamides and a galactose-derived alkyne as precursors. Most of the compounds tested against TcTS showed moderate to weak inhibition (40%-15%), except one of the compounds (81%). Regarding the antitrypanosomal assay, some compounds [(IC50 70.9 µM) and (IC50 44.0 µM)] exhibited the most significant activities, although not as active as benznidazole (IC50 1.4 µM). Nevertheless, the cytotoxicity assessment showed that all compounds were not cytotoxic. In this preliminary work, we considered some compounds as lead scaffolds for further optimization.

Trypanosoma cruzi infection triggers substantial production of nitric oxide (NO), which has been shown to have protective and toxic effects on the host's immune system. Sensing of trypomastigotes by phagocytes activates the inducible NO-synthase (NOS2) pathway, which produces NO and is largely responsible for macrophage-mediated killing of T. cruzi. NO is also responsible for modulating virtually all steps of innate and adaptive immunity. However, NO can also cause oxidative stress, which is especially damaging to the host due to increased tissue damage. The cytokines IFN-³ and TNF-±, as well as chemokines, are strong inducers of NOS2 and are produced in large amounts during T. cruzi acute infection. Conversely, TGF-² and IL-10 negatively regulate NO production. Here we discuss the recent evidence describing the mechanisms by which NO is able to exert its antimicrobial and immune regulatory effects, the mechanisms involved in the oxidative stress response during infection and the implications of NO for the development of therapeutic strategies against T. cruzi.

O estudo foi realizado em quatro remanescentes próximos a cidade de Corumbá, MS (19º05'-19º20' S e 57º40'-57º55' W), com o objetivo de verificar a variação da composição florística e estrutura da floresta decídua em diferentes relevos e tipos de solo. Quatro remanescentes foram amostrados pelo método de quadrantes. Três áreas foram amostradas com 20 pontos, e a quarta área foi amostrada com 50 pontos. Todas as árvores com circunferência à altura do peito > 9 cm foram amostradas. Na floresta estacional decidual aluvial foram amostradas 32 espécies, sendo as de maior valor de importância Attalea phalerata Mart. ex Spreng. (Arecaceae) e Aspidosperma australe Müll. Arg. (Apocynaceae). Nas duas áreas de floresta estacional decidual de terras baixas, foram amostradas 47 e 25 espécies, respectivamente, sendo Sebastiania discolor (Spreng.) Müll. Arg. (Euphorbiaceae) e Phyllostylon rhamnoides (J. Poiss.) Taub. (Ulmaceae) as mais importantes em ambas. No remanescente de floresta estacional decidual submontana foram amostradas 24 espécies, sobressaindo-se Acosmium cardenasii H.S. Irwin & Arroyo (Fabaceae) como a mais importante. A família mais rica nas áreas estudadas foi Fabaceae, com 16 espécies, seguida por Euphorbiaceae, com seis espécies, e por Apocynaceae, Rubiaceae e Sapindaceae, com três espécies cada. As duas áreas de florestas de terras baixas mostraram-se muito similares, tanto na composição florística, como na estrutura. A floresta aluvial apresentou composição florística e estrutura mais distintas das demais áreas. Estes remanescentes de florestas estacionais deciduais apresentaram estrutura e composição florística peculiares, com elementos do chaco e da caatinga, merecendo a intensificação de estudos botânicos e ecológicos.

A survey was made on four deciduous forest remnants in the town of Corumbá, State of Mato Grosso do Sul (19º05'-19º20' S and 57º40'-57º55' W), aiming to verify the floristic and structure variation of deciduous forest remnants in different relief and types of soils. The four remnants were sampled through the point quarter method. Three areas were sampled through 20 points and the fourth area was sampled through 50 points. All trees with circumference at breast height > 9 cm were sampled. In the alluvial deciduous forest, 32 species were sampled, Attalea phalerata Mart. ex Spreng. (Arecaceae) and Aspidosperma australe Müll. Arg. (Apocynaceae) having the highest importance value indexes. In two areas of lowland deciduous forest 47 and 25 species were sampled, respectively; Sebastiania discolor (Spreng.) Müll. Arg. (Euphorbiaceae) and Phyllostylon rhamnoides (J. Poiss.) Taub. (Ulmaceae) being the most important in both. In the remnant of submontane deciduous forest 24 species were sampled, Acosmium cardenasii H.S. Irwin & Arroyo (Fabaceae) outstanding as the main species. The richest family was Fabaceae with 16 species, followed by Euphorbiaceae with six species, and Apocynaceae, Rubiaceae and Sapindaceae with five species each. Both areas of lowland forests showed to be very similar in floristic composition as well as in structure. The alluvial forest presented the most distinct structure and floristic when compared to the other areas. These remnants of deciduous forests have peculiar structure and floristic composition, containing species of the Chaco and Caatinga Provinces that require extensive botanical and ecological studies.

Accidental transmission of Chagas' disease to man by blood transfusion is a serious problem in Latin-America. This paper describes the testing of several synthetic, semi-synthetic, and natural compounds for their activity against blood trypomastigotes in vitro at 4-C. The compounds embody several types of chemical structures: benzoquinone, naphthoquinone, anthracenequinone, phenanthrenequinone, imidazole, piperazine, quinoline, xanthene, and simple benzenic and naphthalenic derivates. Some of them are for the first time tested against Trypanosoma cruzi. The toxic effect these compounds on this parasite was done by two quite distinct sets of experiments. In one set, the compounds were added to infected blood as ethanolic solution. In this situation the most active one was a furan-1, 2-naphthoquinone, in the same range as gentian violet, a new fact to be considered in the assessment of structure-activity relationships in this class of compounds. In other set, we tentatively evaluated the biological activity of water insoluble compounds by adding them in a pure form without solvent into infected blood. In this way some appear to be very active and it was postulated that the effectiveness of such compounds must result from interactions between them and specific blood components.