In vitro and in vivo trypanocidal activity of the ethyl esters of N-allyl and N-propyl oxamates using different Trypanosoma cruzi strains

2007 ◽  
Vol 22 (2) ◽  
pp. 227-233 ◽  
Author(s):  
Charmina Aguirre-Alvarado ◽  
Fabiola Zaragoza-Martínez ◽  
Lorena Rodríguez-Páez ◽  
Benjamín Nogueda ◽  
Isabel Baeza ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Ethyl Esters ◽  
Trypanocidal Activity

scholarly journals In Vitro and In Vivo Studies of the Trypanocidal Activity of Four Terpenoid Derivatives against Trypanosoma cruzi

2012 ◽  
Vol 87 (3) ◽  
pp. 481-488 ◽  
Author(s):  
Inmaculada Ramírez-Macías ◽  
Manuel Sánchez-Moreno ◽  
Enrique Alvarez-Manzaneda ◽  
Ramón Gutierrez-Sánchez ◽  
María José Rosales ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Vivo Studies ◽  
Trypanocidal Activity

scholarly journals Trypanosoma cruzi: in vitro induction of macrophage microbicidal activity.

1978 ◽  
Vol 148 (1) ◽  
pp. 288-300 ◽  
Author(s):  
N Nogueira ◽  
Z A Cohn
Keyword(s):  
Trypanosoma Cruzi ◽  
Spleen Cell ◽  
Peritoneal Macrophages ◽  
Complete Disappearance ◽  
Microbicidal Activity ◽  
Trypanocidal Activity ◽  
Intracellular Parasites ◽  
Normal Spleen

Normal, resident and inflammatory mouse peritoneal macrophages can be induced to display microbicidal activity against trypomastigotes of Trypanosoma cruzi by exposure to products from antigen-pulsed, sensitized spleen cell populations. Optimal macrophage microbicidal activity was achieved by constant exposure and daily renewal of the spleen cell factors. Macrophages obtained after an intraperitoneal injection of mild inflammatory agents were rapidly induced, displaying trypanocidal activity 24 h after exposure to the active spleen cell factor(s), and by 48 h, parasites were no longer observed. Resident peritoneal macrophages required 24 h longer for activation. Removal of the factor(s) before achieving complete disappearance of intracellular parasites led to resumed growth of the surviving organisms. The spleen cell factor(s) is effective when added either before or after exposure of the macrophages to trypomastigotes, and does not itself alter parasite viability. Dilution of the factor(s) up to 1:16 still results in significant trypanocidal activity. In vivo activated cells, obtained after a specific secondary challenge of animals infected with T. cruzi or Bacille Calmette-Guérin, lose their trypanocidal activity under in vitro conditions. This loss of activity can be prevented or restored by the addition of the active spleen cell factor(s). Induction of trypanocidal activity is also obtained with products from Concanavalin A- or lipopolysaccharide-stimulated normal spleen cells.

IN VITRO and IN VIVO TRYPANOCIDAL ACTIVITY OF A BENZOFUROXAN DERIVATIVE AGAINST Trypanosoma cruzi

2021 ◽  
pp. 108125
Author(s):  
Letícia dos Santos Petry ◽  
João Cândido Pillar Mayer ◽  
Marjorie de Giacommeti ◽  
Dionatan Teixeira de Oliveira ◽  
Litiérria Razia Garzon ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Trypanocidal Activity

scholarly journals Activation of macrophages in vivo and in vitro. Correlation between hydrogen peroxide release and killing of Trypanosoma cruzi.

1979 ◽  
Vol 149 (5) ◽  
pp. 1056-1068 ◽  
Author(s):  
C Nathan ◽  
N Nogueira ◽  
C Juangbhanich ◽  
J Ellis ◽  
Z Cohn
Keyword(s):  
Trypanosoma Cruzi ◽  
Peritoneal Macrophages ◽  
Trypanocidal Activity ◽  
Dose Dependent Fashion ◽  
Hydrogen Peroxide Release ◽  
Inflammatory Macrophages ◽  
Dose Dependent ◽  
Mouse Peritoneal Macrophages

As reported previously, mouse peritoneal macrophages could be activated to kill intracellular trypomastigotes of Trypanosoma cruzi, the agent of Chagas' disease, in either of two ways: by immunizing and boosting the mice (3), or by culturing resident or inflammatory macrophages in spleen cell factor(s) (SCF) in vitro (2). Macrophages activated in vivo became less trypanocidal with time in culture, and cells activated in vitro lost trypanocidal capacity when CSF was removed (2). In the present study, the ability of macrophages to release H2O2 in response to phorbol myristate acetate (PMA) could be induced in vivo and in vitro, and reversed in vitro, in a manner correlating closely with changes in trypanocidal activity. Macrophages could be activated in vitro with SCF in a time-dependent and dose-dependent fashion, so that they released as much H2O2 as macrophages activated in vivo. The sensitivity of epimastigotes and trypomastigotes to enzymatically generated H2O2 suggested that the generation of H2O2 by activated macrophages could be plausible explanation for their trypanocidal activity. Of the biochemical correlates of macrophage activation reported to date, increased ability to release H2O2 seems most closely allied to enhanced capacity to kill an intracellular pathogen.

In vitro and in vivo trypanocidal activity of some benzimidazole derivatives against two strains of Trypanosoma cruzi

Acta Tropica ◽  
2012 ◽  
Vol 122 (1) ◽  
pp. 108-112 ◽  
Author(s):  
Dylan L. Díaz-Chiguer ◽  
Adrián Márquez-Navarro ◽  
Benjamín Nogueda-Torres ◽  
Gloria de la Luz León-Ávila ◽  
Jaime Pérez-Villanueva ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Benzimidazole Derivatives ◽  
Trypanocidal Activity

scholarly journals Experimental Chemotherapy against Trypanosoma cruzi Infection Using Ruthenium Nitric Oxide Donors

2009 ◽  
Vol 53 (10) ◽  
pp. 4414-4421 ◽  
Author(s):  
Jean Jerley N. Silva ◽  
Wander R. Pavanelli ◽  
José Clayston M. Pereira ◽  
João S. Silva ◽  
Douglas W. Franco
Keyword(s):  
Trypanosoma Cruzi ◽  
Triethyl Phosphite ◽  
Dose Effect ◽  
No Donors ◽  
Trypanocidal Activity ◽  
Effective Doses ◽  
Acute Chagas Disease ◽  
Cruzi Infection

ABSTRACT The ruthenium NO donors of the group trans-[Ru(NO)(NH3)4L] n+, where the ligand (L) is N-heterocyclic H2O, SO3 2−, or triethyl phosphite, are able to lyse Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory concentrations against bloodstream trypomastigotes (IC50 try) and cytotoxicity data on mammalian V-79 cells (IC50 V79), the in vitro therapeutic indices (TIs) (IC50 V79/IC50 try) for these compounds were calculated. Compounds that exhibited an in vitro TI of ≥10 and trypanocidal activity against both epimastigotes and trypomastigotes with an IC50 try/epi of ≤100 μM were assayed in a mouse model for acute Chagas' disease, using two different routes (intraperitoneal and oral) for drug administration. A dose-effect relationship was observed, and from that, the ideal dose of 400 nmol/kg of body weight for both trans-[Ru(NO)(NH3)4isn](BF4)3 (isn, isonicotinamide) and trans-[Ru(NO)(NH3)4imN](BF4)3 (imN, imidazole) and median (50%) effective doses (ED50) of 86 and 190 nmol/kg, respectively, were then calculated. Since the 50% lethal doses (LD50) for both compounds are higher than 125 μmol/kg, the in vivo TIs (LD50/ED50) of the compounds are 1,453 for trans-[Ru(NO)(NH3)4isn](BF4)3 and 658 for trans-[Ru(NO)(NH3)4imN](BF4)3. Although these compounds exhibit a marked trypanocidal activity and are able to react with cysteine, they exhibit very low activity in T. cruzi-glycosomal glyceraldehyde-3-phosphate dehydrogenase tests, suggesting that this enzyme is not their target. The trans-[Ru(NO)(NH3)4isn](BF4)3 and trans-[Ru(NO)(NH3)4imN](BF4)3 compounds are able to eliminate amastigote nests in myocardium tissue at 400-nmol/kg doses and ensure the survival of all infected mice, thus opening a novel set of therapies to try against trypanosomatids.

Unusual dimeric flavonoids from Arrabidaea brachypoda with very significant in vitro and in vivo anti-Trypanosoma cruzi activity

Planta Medica ◽  
2014 ◽  
Vol 80 (16) ◽  
Author(s):  
C Quitino-da-Rocha ◽  
E Ferreira-Queiroz ◽  
C Santana-Meira ◽  
DR Magalhães-Moreira ◽  
M Botelho-Pereira-Soares ◽  
...  
Keyword(s):  
Trypanosoma Cruzi

scholarly journals Neurotrophin Receptor TrkC Is an Entry Receptor for Trypanosoma cruzi in Neural, Glial, and Epithelial Cells

2011 ◽  
Vol 79 (10) ◽  
pp. 4081-4087 ◽  
Author(s):  
Craig Weinkauf ◽  
Ryan Salvador ◽  
Mercio PereiraPerrin
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Mammalian Cells ◽  
Chinese Hamster ◽  
Neuronal Cell ◽  
Host Cells ◽  
Neurotrophin Receptor ◽  
Content Type

ABSTRACTTrypanosoma cruzi, the agent of Chagas' disease, infects a variety of mammalian cells in a process that includes multiple cycles of intracellular division and differentiation starting with host receptor recognition by a parasite ligand(s). Earlier work in our laboratory showed that the neurotrophin-3 (NT-3) receptor TrkC is activated byT. cruzisurfacetrans-sialidase, also known as parasite-derived neurotrophic factor (PDNF). However, it has remained unclear whether TrkC is used byT. cruzito enter host cells. Here, we show that a neuronal cell line (PC12-NNR5) relatively resistant toT. cruzibecame highly susceptible to infection when overexpressing human TrkC but not human TrkB. Furthermore,trkCtransfection conferred an ∼3.0-fold intracellular growth advantage. Sialylation-deficient Chinese hamster ovarian (CHO) epithelial cell lines Lec1 and Lec2 also became much more permissive toT. cruziafter transfection with thetrkCgene. Additionally, NT-3 specifically blockedT. cruziinfection of the TrkC-NNR5 transfectants and of naturally permissive TrkC-bearing Schwann cells and astrocytes, as did recombinant PDNF. Two specific inhibitors of Trk autophosphorylation (K252a and AG879) and inhibitors of Trk-induced MAPK/Erk (U0126) and Akt kinase (LY294002) signaling, but not an inhibitor of insulin-like growth factor 1 receptor, abrogated TrkC-mediated cell invasion. Antibody to TrkC blockedT. cruziinfection of the TrkC-NNR5 transfectants and of cells that naturally express TrkC. The TrkC antibody also significantly and specifically reduced cutaneous infection in a mouse model of acute Chagas' disease. TrkC is ubiquitously expressed in the peripheral and central nervous systems, and in nonneural cells infected byT. cruzi, including cardiac and gastrointestinal muscle cells. Thus, TrkC is implicated as a functional PDNF receptor in cell entry, independently of sialic acid recognition, mediating broadT. cruziinfection bothin vitroandin vivo.

scholarly journals In Vitro and In Vivo Activities of E5700 and ER-119884, Two Novel Orally Active Squalene Synthase Inhibitors, against Trypanosoma cruzi

2004 ◽  
Vol 48 (7) ◽  
pp. 2379-2387 ◽  
Author(s):  
Julio A. Urbina ◽  
Juan Luis Concepcion ◽  
Aura Caldera ◽  
Gilberto Payares ◽  
Cristina Sanoja ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Public Health Problem ◽  
Squalene Synthase ◽  
Host Cells ◽  
In Vivo Studies ◽  
Inorganic Pyrophosphate ◽  
Orally Active

ABSTRACT Chagas' disease is a serious public health problem in Latin America, and no treatment is available for the prevalent chronic stage. Its causative agent, Trypanosoma cruzi, requires specific endogenous sterols for survival, and we have recently demonstrated that squalene synthase (SQS) is a promising target for antiparasitic chemotherapy. E5700 and ER-119884 are quinuclidine-based inhibitors of mammalian SQS that are currently in development as cholesterol- and triglyceride-lowering agents in humans. These compounds were found to be potent noncompetitive or mixed-type inhibitors of T. cruzi SQS with K i values in the low nanomolar to subnanomolar range in the absence or presence of 20 μM inorganic pyrophosphate. The antiproliferative 50% inhibitory concentrations of the compounds against extracellular epimastigotes and intracellular amastigotes were ca. 10 nM and 0.4 to 1.6 nM, respectively, with no effects on host cells. When treated with these compounds at the MIC, all of the parasite's sterols disappeared from the parasite cells. In vivo studies indicated that E5700 was able to provide full protection against death and completely arrested the development of parasitemia when given at a concentration of 50 mg/kg of body weight/day for 30 days, while ER-119884 provided only partial protection. This is the first report of an orally active SQS inhibitor that is capable of providing complete protection against fulminant, acute Chagas' disease.

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