scholarly journals Trypanocidal activity of the phenyl-substituted analogue of furamidine DB569 against Trypanosoma cruzi infection in vivo

2006 ◽  
Vol 58 (3) ◽  
pp. 610-614 ◽  
Author(s):  
E. M. de Souza
Keyword(s):  
Trypanosoma Cruzi ◽  
Trypanocidal Activity ◽  
Cruzi Infection

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.

scholarly journals Benznidazole Treatment following Acute Trypanosoma cruzi Infection Triggers CD8+ T-Cell Expansion and Promotes Resistance to Reinfection

2002 ◽  
Vol 46 (12) ◽  
pp. 3790-3796 ◽  
Author(s):  
Bianca Perdigão Olivieri ◽  
Vinícius Cotta-de-Almeida ◽  
Tania Araújo-Jorge
Keyword(s):  
T Lymphocytes ◽  
Trypanosoma Cruzi ◽  
Immune Regulation ◽  
Immune Dysregulation ◽  
Direct Role ◽  
Parasite Replication ◽  
The Impact ◽  
Shed Light ◽  
Cruzi Infection

ABSTRACT Many studies have shed light on the mechanisms underlying both immunoprotection and immune dysregulation arising after Trypanosoma cruzi infection. However, little is known about the impact of benznidazole (N-benzyl-2-nitroimidazole acetamide), the drug available for clinical treatment of the infection, on the immune system in the infected host. In the present study we investigated the effect of benznidazole therapy on the lymphoid compartment during the course of experimental T. cruzi infection. Although amelioration of a variety of clinical and parasitological signs was observed in treated mice, amelioration of splenocyte expansion was not detected. Interestingly, this sustained splenomegaly observed in benznidazole-treated mice showed a preferential expansion of CD8+ T lymphocytes. Moreover, although benznidazole treatment blocked the expansion of recently activated CD4+ and CD8+ T cells seen in infected hosts, benznidazole treatment led to a selective expansion of effector and memory CD8+ T lymphocytes in association with a lower rate of apoptosis. In addition, the surviving treated animals were protected from reinfection. Together, these data suggest that, in addition to its well-known direct role in blocking parasite replication in vivo, benznidazole appears to directly affect immune regulation in T. cruzi-infected hosts.

scholarly journals A Parent-of-Origin Effect Determines the Susceptibility of a Non-Informative F1 Population to Trypanosoma cruzi Infection In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e56347 ◽  
Author(s):  
Grace K. Silva ◽  
Larissa D. Cunha ◽  
Catarina V. Horta ◽  
Alexandre L. N. Silva ◽  
Fredy R. S. Gutierrez ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Parent Of Origin ◽  
Origin Effect ◽  
Cruzi Infection

New 1,2,3-triazole-based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

2018 ◽  
Vol 92 (3) ◽  
pp. 1670-1682 ◽  
Author(s):  
Débora Inácio Leite ◽  
Fábio de Vasconcellos Fontes ◽  
Monica Macedo Bastos ◽  
Lucas Villas Boas Hoelz ◽  
Maria da Conceição Avelino Dias Bianco ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Cruzi Infection

In vitro and in vivo activity of voriconazole and benznidazole combination on trypanosoma cruzi infection models

Acta Tropica ◽  
2020 ◽  
Vol 211 ◽  
pp. 105606
Author(s):  
Julián Ernesto Nicolás Gulin ◽  
Mackenzie Anne Eagleson ◽  
Rodrigo A. López-Muñoz ◽  
María Elisa Solana ◽  
Jaime Altcheh ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Infection Models ◽  
Cruzi Infection

Resistance to Trypanosoma cruzi infection in mice does not necessarily correlate with production of interferon- g in vivo

1998 ◽  
Vol 187 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Christian Meyer zum Büschenfelde ◽  
Sven Cramer ◽  
B. Fleischer ◽  
Stefanie Frosch
Keyword(s):  
Trypanosoma Cruzi ◽  
Cruzi Infection

Drug repurposing strategy against Trypanosoma cruzi infection: In vitro and in vivo assessment of the activity of metronidazole in mono- and combined therapy

2017 ◽  
Vol 145 ◽  
pp. 46-53 ◽  
Author(s):  
M.R. Simões-Silva ◽  
J.S. De Araújo ◽  
G.M. Oliveira ◽  
K.C. Demarque ◽  
R.B. Peres ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Combined Therapy ◽  
Drug Repurposing ◽  
Cruzi Infection ◽  
In Vivo Assessment

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 Optimization of 1,4-Naphthoquinone Hit Compound: A Computational, Phenotypic, and In Vivo Screening against Trypanosoma cruzi

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 423
Author(s):  
Leonardo S. Lara ◽  
Guilherme C. Lechuga ◽  
Caroline dos S. Moreira ◽  
Thaís B. Santos ◽  
Vitor F. Ferreira ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Acute Infection ◽  
Public Health Problem ◽  
Parasite Load ◽  
Relevant Information ◽  
Trypanocidal Activity ◽  
Structure Activity ◽  
Activity Structure ◽  
Sas Maps

Chagas disease (CD) still represents a serious public health problem in Latin America, even after more than 100 years of its discovery. Clinical treatments (nifurtimox and benznidazole) are considered inadequate, especially because of undesirable side effects and low efficacy in the chronic stages of the disease, highlighting the urgency for discovering new effective and safe drugs. A small library of compounds (1a–i and 2a–j) was designed based on the structural optimization of a Hit compound derived from 1,4-naphthoquinones (C2) previously identified. The biological activity, structure-activity relationship (SAR), and the in silico physicochemical profiles of the naphthoquinone derivatives were analyzed. Most modifications resulted in increased trypanocidal activity but some substitutions also increased toxicity. The data reinforce the importance of the chlorine atom in the thiophenol benzene ring for trypanocidal activity, highlighting 1g, which exhibit a drug-likeness profile, as a promising compound against Trypanosoma cruzi. SAR analysis also revealed 1g as cliff generator in the structure-activity similarity map (SAS maps). However, compounds C2 and 1g were unable to reduce parasite load, and did not prevent mouse mortality in T. cruzi acute infection. Phenotypic screening and computational analysis have provided relevant information to advance the optimization and design of new 1,4-naphthoquinone derivatives with a better pharmacological profile.

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