Plant metabolites active against Trypanosoma cruzi

Parasitic diseases are widespread in less developed countries, and are a major cause of suffering and inability of the affected populations to improve their own living conditions. Among these diseases, American trypanosomiasis (Chagas' disease), due to the kinetoplastid protozoon Trypanosoma cruzi, is particularly relevant to Latin America. The natural products literature mentions a wide variety of isolated substances showing activity against this parasite. Although some of these compounds appear to be promising leads, their potential is presently limited by the need of high concentrations, unfavorable pharmacokinetics, and/or by their low solubility in blood. Their mechanisms of action are unknown in most cases, although some trends appear to be emerging. This review presents and discusses the data available until mid-1995

SINTESIS DE 2.ARIL.1,3.DINITROPROPANOS, INTERMEDIARIOS PARA LA OBTENCION DE NUEVOS ANTIDEPRESIVOS

Se describe la síntesis de una serie de 2-aril-l,3-dinitropropanos por condensación de benzaldehidos con nitrometano. Estos compuestos tienen utilidad potencial como precursores de 2-aril-1,3-dinitropropanos, los que a su vez ocupan un lugar central en la vía que conduce a las 2-amino-5-aril-1,4,5,6-tetrahidropirimidinas antidepresi vas

A novel route to 5,7-dimethoxy-6-hydroxyflavone

A novel route to 5,7-dimethoxy-6-hydroxyflavone is described, involving the cyclization of an intermediate phosphorane as the key step

Structure–activity relationship studies of flavonoids as potent inhibitors of human platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2

Human lipoxygenase (hLO) isozymes have been implicated in a number of disease states and have attracted much attention with respect to their inhibition. One class of inhibitors, the flavonoids, have been shown to be potent lipoxygenase inhibitors but their study has been restricted to those compounds found in nature, which have limited structural variability. We have therefore carried out a comprehensive study to determine the structural requirements for flavonoid potency and selectivity against platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. We conclude from this study that catechols are essential for high potency, that isoflavones and isoflavonones tend to select against 12-hLO, that isoflavons tend to select against 15-hLO-1, but few flavonoids target 15-hLO-2

MAO inhibition by arylisopropylamines: the effect of oxygen substituents at the b-position

Abstract—Twenty-nine arylisopropylamines, substituted at the b-position of their side chain by an oxo, hydroxy, or methoxy group, were evaluated in vitro as MAO-A and MAO-B inhibitors. The oxo derivatives (‘cathinones’) were in general less active as MAO-A inhibitors than the corresponding arylisopropylamines, but exhibited an interesting MAO-B inhibiting activity, which was absent in the hydroxy, methoxy, and b-unsubstituted analogues. These results suggest that selective affinity for the two MAO isoforms in this family of compounds is modulated not only by the aryl substitution pattern but also by the side-chain substituents on the arylalkylamine scaffold.This work was supported by FONDECYT grant No. 1000776 and MECESUP-USA0007 project

In vitro activity of thienyl-2-nitropropene compounds against Trypanosoma cruzi

The in vitro activity of four 2-nitropropene derivatives, 1-(3-benzothienyl)-2-nitropropene (N1), 1-(3-thienyl)-2-nitropropene (N2), 1-(5-bromo-2-thienyl)-2-nitropropene (N3) and 1-(4-bromo-2-thienyl)-2-nitropropene (N4), were tested against cultures of the parasite Trypanosoma cruzi . Cytotoxicity studies were performed using Vero cells. The blood trypomastigotes, amastigotes and epimastigotes showed differential degrees of sensitivity towards the four tested compounds; the highest activity against the epimastigotes and blood tripomastigotes was exhibited by N1, followed by N3, N4 and finally N2. In contrast, whereas the compounds N1, N3 and N4 exerted similar magnitudes of activity against amastigotes, N2 was found to be a much less potent compound. According to our results, the compound N1 had the highest level of activity (IC50: 0.6 μM) against epimastigotes