Search results for "Trypanosoma cruzi."
showing 7 items of 37 documents
Chemoenzymatic Synthesis of Functional Sialyl LewisX Mimetics with a Heteroaromatic Core
2014
Functional mimetics of the sialyl Lewis(X) tetrasaccharide were prepared by the enzymatic sialylation of a 1,3-diglycosylated indole and a glycosyl azide, which was subsequently transformed into a 1,4-diglycosylated 1,2,3-triazole, by using the trans-sialidase of Trypanosoma cruzi. These compounds inhibited the binding of E-, L-, and P-selectin-coated nanoparticles to polyacrylamide-bound sialyl-Lewis(X) -containing neighboring sulfated tyrosine residues (sTyr/sLe(X) -PAA) at low or sub-millimolar concentrations. Except for E-selectin, the mimetics showed higher activities than the natural tetrasaccharide.
In vitro and in vivo antileishmanial and trypanocidal studies of new N-benzene- and N-naphthalenesulfonamide derivatives.
2013
We report in vivo and in vitro antileishmanial and trypanocidal activities of a new series of N-substituted benzene and naphthalenesulfonamides 1-15. Compounds 1-15 were screened in vitro against Leishmania infantum , Leishmania braziliensis , Leishmania guyanensis , Leishmania amazonensis , and Trypanosoma cruzi . Sulfonamides 6e, 10b, and 10d displayed remarkable activity and selectivity toward T. cruzi epimastigotes and amastigotes. 6e showed significant trypanocidal activity on parasitemia in a murine model of acute Chagas disease. Moreover, 6e, 8c, 9c, 12c, and 14d displayed interesting IC50 values against Leishmania spp promastigotes as well as L. amazonensis and L. infantum amastigot…
New ligand-based approach for the discovery of antitrypanosomal compounds.
2005
The antitrypanosomal activity of 10 already synthesized compounds was in silico predicted as well as in vitro and in vivo explored against Trypanosoma cruzi. For the computational study, an approach based on non-stochastic linear fingerprints to the identification of potential antichagasic compounds is introduced. Molecular structures of 66 organic compounds, 28 with antitrypanosomal activity and 38 having other clinical uses, were parameterized by means of the TOMOCOMD-CARDD software. A linear classification function was derived allowing the discrimination between active and inactive compounds with a confidence of 95%. As predicted, seven compounds showed antitrypanosomal activity (%AE > 7…
Application of molecular topology to the prediction of inhibition of Trypanosoma cruzi Hexokinase by bisphosphonates
2008
Se ha desarrollado un modelo topológico-matemático para la búsqueda de nuevos derivados bisfosfonatos activos frente a la hexokinasa de Trypanosoma cruzi. Utilizando el análisis lineal discriminante se ha seleccionado una función con cuatro variables capaz de predecir adecuadamente la CI50 para cada compuesto de las series de entrenamiento y test. El modelo propuesto se ha aplicado a una librería molecular y se han propuesto nuevas estructuras potencialmente activas frente a T. cruzi.
Computational discovery of novel trypanosomicidal drug-like chemicals by using bond-based non-stochastic and stochastic quadratic maps and linear dis…
2009
Herein we present results of a quantitative structure-activity relationship (QSAR) studies to classify and design, in a rational way, new antitrypanosomal compounds by using non-stochastic and stochastic bond-based quadratic indices. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop QSAR models based on linear discriminant analysis (LDA). Non-stochastic model correctly classifies more than 93% and 95% of chemicals in both training and external prediction groups, respectively. On the other hand, the stochastic model shows an accuracy of about the 87% for both series. As an experiment of virtual lead generation, the …
The catalytic mechanism of glyceraldehyde 3-phosphate dehydrogenase from Trypanosoma cruzi elucidated via the QM/MM approach
2013
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been identified as a key enzyme involved in glycolysis processes for energy production in the Trypanosoma cruzi parasite. This enzyme catalyses the oxidative phosphorylation of glyceraldehyde 3-phosphate (G3P) in the presence of inorganic phosphate (Pi) and nicotinamide adenosine dinucleotide (NAD+). The catalytic mechanism used by GAPDH has been intensively investigated. However, the individual roles of Pi and the C3 phosphate of G3P (Ps) sites, as well as some residues such as His194 in the catalytic mechanism, remain unclear. In this study, we have employed Molecular Dynamics (MD) simulations within hybrid quantum mechanical/molecular …
Synthetic single and double aza-scorpiand macrocycles acting as inhibitors of the antioxidant enzymes iron superoxide dismutase and trypanothione red…
2014
The anti-chagasic activity of a series of eleven derivatives of aza-scorpiand-like macrocycles, some of them newly synthesised, was assayed. The four compounds with the best selectivity indices in vitro were subjected to in vivo assays. Tests in a murine model of the acute phase of Chagas disease showed a two-fold reduction in parasitaemia compared to that with benznidazole. Furthermore, compounds 7 and 11, with 4-pyridine and phenanthroline substituents in the lateral chain, caused a remarkable decrease in parasitaemia reactivation during the chronic phase after inducing immunosuppression in mice. These activity studies were complemented by measuring their inhibitory effect towards the ant…