Glycosomal Targets for Anti-Trypanosomatid Drug Discovery

Glycosomes are peroxisome-related organelles found in all kinetoplastid protists, including the human pathogenic species of the family Trypanosomatidae: Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. Glycosomes are unique in containing the majority of the glycolytic/gluconeogenic enzymes, but they also possess enzymes of several other important catabolic and anabolic pathways. The different metabolic processes are connected by shared co-factors and some metabolic intermediates, and their relative importance differs between the parasites or their distinct life-cycle stages, dependent on the environmental conditions encountered. By genetic or chemical means, a variety of glycosomal enzymes participating in different processes have been validated as drug targets. For several of these enzymes, as well as others that are likely crucial for proliferation, viability or virulence of the parasites, inhibitors have been obtained by different approaches such as compound libraries screening or design and synthesis. The efficacy and selectivity of some initially obtained inhibitors of parasite enzymes were further optimized by structure-activity relationship analysis, using available protein crystal structures. Several of the inhibitors cause growth inhibition of the clinically relevant stages of one or more parasitic trypanosomatid species and in some cases exert therapeutic effects in infected animals. The integrity of glycosomes and proper compartmentalization of at least several matrix enzymes is also crucial for the viability of the parasites. Therefore, proteins involved in the assembly of the organelles and transmembrane passage of substrates and products of glycosomal metabolism offer also promise as drug targets. Natural products with trypanocidal activity by affecting glycosomal integrity have been reported.

Alkyl Caffeates as Anti-Helicobacter Pylori and Scavenger of Oxidants Produced by Neutrophils

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hypusine Modification of the Ribosome-binding Protein eIF5A, a Target for New Anti-Inflammatory Drugs: Understanding the Action of the Inhibitor GC7 on a Murine Macrophage Cell Line

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Peptide Prodrugs for the Treatment of CNS Disorders: A Perspective for New Drugs

The treatment of central nervous system (CNS) diseases is a major challenge. The presence of the barrier intended to protect the brain from unwanted molecules also impairs the efficacy of CNS-targeted drugs. The discovery of drug targets for CNS diseases opens a door for the selective treatment of these diseases. However, the physicochemical properties of drugs, including their hydrophilic properties and their peripheral metabolism, as well as the blood-brain barrier, can adversely affect the therapeutic potential of CNS-targeted drugs. Although peptides are often metabolized by enzymes, they are of particular interest for the treatment of CNS diseases or as carriers to deliver drugs to the brain. In this review, we discuss the use of peptides as potential prodrugs for the treatment of CNS diseases.

Microbiological Assay for the Determination of Colistin Sulphate

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Inhibition of Lysozyme by Taurine Dibromamine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

O tema da paz perpétua

This paper presents an analytical study of the theory of perpetual peace, examining its various formulations from sixteenth century to nineteenth century, especially the Enlightenment theories of Saint-Pierre, Rousseau, Bentham and Kant, and nineteenth-century criticism of Hegel, Marx and Engels.

Diversity and Localization of Bacterial Endosymbionts from Whitefly Species Collected in Brazil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Use of Guanidine Compounds in the Treatment of Neglected Tropical Diseases

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Physical Exercise in MCI Elderly Promotes Reduction of Pro-Inflammatory Cytokines and Improvements on Cognition and BDNF Peripheral Levels

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Molecular markers of angiogenesis and metastasis in lines of oral carcinoma after treatment with melatonin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

O papel da serapilheira no desenvolvimento inicial de mudas de espécies florestais nativas

A serapilheira de matas e florestas é rica em matéria orgânica e responsável pela ciclagem de nutrientes que ocorre neste ecossistema. Além de atuar como protetora do solo e habitat para diversos microrganismos e insetos. O presente estudo buscou analisar o papel da serapilheira no desenvolvimento de mudas florestais nativas em viveiros. As espécies utilizadas no experimento foram Parapitadenia rigida (Benth) (angico-vermelho), Acacia polyphylla DC. (monjoleiro), Lonchocarpus muehlbergianus Hassl. (embira-de-sapo) e Schizolobium parahyba (Vell.)S.F.Blake (guapuruvu). O crescimento foi analisado em quatro substratos: mineral (S1), mineral com serapilheira na proporção de volume 1:1 (S2), orgânico usado em viveiros (S3) e orgânico usado em viveiros com serapilheira na proporção de volume 1:1 (S4). O delineamento experimental consistiu em blocos ao acaso com 16 tratamentos e 5 repetições. Durante uma primeira fase foram feitas as medições de altura e diâmetro das mudas em fase de viveiro. A segunda fase foi a análise da biomassa seca e avaliação da sobrevivência inicial em campo. O resultado apresentou melhores desempenhos no crescimento e sobrevivência nos tratamentos com serapilheira em comparação aos sem serapilheira. Podemos concluir que a serapilheira apresenta potenciais benéficos relevantes para a produção de mudas florestais

A pedagogia das competências: estudo de caso em um curso de tecnologia da UTFPR

Pós-graduação em Educação - FFC

Atributos do solo e flora infestante em sistema de semeadura direta do milho na palha de leguminosas arbóreas

Pós-graduação em Agronomia (Ciência do Solo) - FCAV

Greenhouse gas balance in the conversion from extensive pasture to other agricultural systems in Andean region of Colombia

Pós-graduação em Agronomia (Ciência do Solo) - FCAV