Combination therapy with benznidazole and doxycycline shows no additive effect to monotherapy with benznidazole in mice infected with the VL-10 strain of the Trypanosoma cruzi

Carneiro, Ana Cláudia Alvarenga; Costa, G.; Ferreira, Cyntia Silva; Ramos, Isalira Peroba; Sarandy, Mariáurea Matias; Leite, Ana; Menezes, Ana Paula de Jesus; Silva, B.M.; Nogueira, Katiane O.P.C.; Carvalho, Antônio Carlos Campos de; Gonçalves, Reggiani Vilela; Talvani, André

doi:10.1016/j.ijcard.2019.07.047

Cited by 6 publications

(3 citation statements)

References 28 publications

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“…Anti‐ T. cruzi activities of 1 – 6 were evaluated in vitro against trypomastigote forms of the parasite, using benznidazole as positive control [32,33] . As presented in Table 1, all tested compounds exhibited activity with EC 50 ranging from 45.2 to 3.6 μM.…”

Section: Resultsmentioning

confidence: 99%

γ‐Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

Reis

Umehara

Conceição

et al. 2021

Chemistry & Biodiversity

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In the present study, five known γ‐lactones (majoranolide B – 1, majorenolide – 2, majorynolide – 3, lincomolide D – 4, and isolinderanolide E – 5), as well as a new one (perseanolide – 6), were isolated from Persea fulva and P. americana. All isolated compounds exhibited potential activity against trypomastigote forms of Trypanosoma cruzi, whereas compounds 2 (EC50 of 4.8 μM) and 6 (EC50 of 3.6 μM) displayed superior activity than the positive control benznidazole (EC50 of 16.4 μM), with selectivity index (SI) values of 17.8 and >55.6, respectively (benznidazole, SI>12.2). Molecular docking studies were performed for 1–6 against six T. cruzi molecular targets. Using this approach, we observed that, even though perseanolide (6) showed favorable docking to several studied targets, the results were especially promising for hypoxanthine phosphoribosyl transferase (PDB 1TC1). As PDB 1TC1 is associated to the transference of a monophosphorylated ribose from phosphoribosylpyrophosphate (PRPP) in the ribonucleotide synthesis pathway, this interaction may affect the survival of T. cruzi in mammalian cells. The data herein also indicate that possible intermolecular interactions between 6 and PDB 1TC1 derive from (i) hydrogen bonds in the α,β‐unsaturated‐γ‐lactone unity and (ii) hydrophobic interactions in the long‐chain alkyl group. Based on our results, perseanolide (6), reported for the first time in this work, can auspiciously contribute to future works regarding new trypanocidal agents.

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Section: Resultsmentioning

confidence: 99%

γ‐Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

Reis

Umehara

Conceição

et al. 2021

Chemistry & Biodiversity

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“…High variability of GRS is still a recognized problem of the technique that can be explained by several factors, such as image formation and tracking of speckles 31 . However, we should also consider inflammation as a more prominent mechanism of acute CD 32 than myocardial fibrosis, and also question if GCS and GRS can demonstrate it.…”

Section: Discussionmentioning

confidence: 99%

Prospective study of ventricular function and myocardial deformation related to survival in acute Chagas disease: an experimental animal model

Vargas

Dias

Moreira

et al. 2021

Rev. Inst. Med. trop. S. Paulo

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Chagas disease (CD) has been changing from an endemic Latino-American disease to a condition found outside endemic regions, due to migratory movements. Although often subclinical, its acute phase can be lethal. This study aimed to assess survival during the acute phase of CD and its relationship with ventricular function in an experimental model. To this end, 30 Syrian hamsters were inoculated with Trypanosoma cruzi (IG) and other 15 animals received saline solution (CG). Groups were monitored daily and submitted to echocardiography in two moments: before the challenge and 15 days post-infection. Left ventricular ejection fraction (LVEF) and global longitudinal myocardial strain (GLS) of the LV were measured. The IG was divided into groups of animals with and without clinical signs of disease. ANOVA for mixed models was used to compare ventricular function parameters. Survival analysis was studied using Kaplan-Meier curves and the log-rank test. The follow-up lasted 60 days. LVEF in IG was reduced through time (53.80 to 43.55%) compared to CG (57.86 to 59.73%) (p=0.002). There was also a reduction of GLS (−18.97% to −12.44%) in the IG compared to CG (p=0.012). Twelve animals from IG died compared to one animal from CG. Eleven out of the 12 animals from the IG group died before presenting with clinical signs of infection. Survival was reduced in the IG compared to CG over time (p=0.02). The reduced survival during the acute phase of this experimental model of Chagas disease was related to the significant reduction of LV function. The mortality rate in the IG was higher in the group presenting with clinical signs of infection.

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“…Se ha demostrado que el modelo murino puede desarrollar cardiomiopatía dilatada tras la infección por T. cruzi. En este modelo animal, se han podido observar por ecocardiografía anormalidades en la función sistólica (33), gasto cardíaco e incremento en la masa del ventrículo izquierdo con dilatación ventricular (Figura 3) (17,(34)(35)(36). Es importante mencionar que, en el caso de animales de experimentación, todas las técnicas de imagen anteriormente mencionadas requieren de la inmovilización del modelo de estudio para evitar artefactos de movimiento durante la adquisición de las imágenes (16,27,29).…”

Section: Ecografíaunclassified

Aplicaciones y potencial de las técnicas de diagnóstico por imagen en la investigación biomédica de la enfermedad de Chagas

Haro¹,

Hevia–Montiel²,

López-Blanco³

et al. 2021

Rev Biomed

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Las técnicas de diagnóstico por imagen son métodos no invasivos o mínimamente invasivos que permiten la visualización de órganos internos y el estudio de su función. Incluyen la ecografía, radiología, tomografía computarizada, resonancia magnética y medicina nuclear, entre otras. El diagnóstico por imagen se ha convertido en un componente esencial en las investigaciones científicas que requieren el seguimientoin vivo de cambios patológicos. En esta revisión, presentamos estas técnicas y sus aplicaciones para el estudio de la infección por Trypanosoma cruzi, parásito causante de la enfermedad de Chagas; con énfasis en la ecografía, la técnica más ampliamente empleada por su bajo costo y la única que proporciona imágenes en tiempo real. La ecografía se utiliza actualmente en el Centro de Investigaciones Regionales “Dr. Hideyo Noguchi” de la Universidad Autónoma de Yucatán, para el estudio de la infección por T. cruzien el modelo murino. Ha demostrado ser útil para la evaluación in vivodecambios morfológicos y funcionales del corazón, el estudio de la progresión de la infección y la efectividad de nuevos fármacos. Adicionalmente, las imágenes obtenidas nos han permitido el desarrollo de sistemas automatizados auxiliares en el diagnóstico de la infección, los cuales se encuentran en fase experimental. La ecografía es útil para responder preguntas que aún permanecen sin explorar sobre la enfermedad de Chagas como, el estudio de la progresión del daño órganos durante la infección.

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Combination therapy with benznidazole and doxycycline shows no additive effect to monotherapy with benznidazole in mice infected with the VL-10 strain of the Trypanosoma cruzi

Cited by 6 publications

References 28 publications

γ‐Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

γ‐Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

Prospective study of ventricular function and myocardial deformation related to survival in acute Chagas disease: an experimental animal model

Aplicaciones y potencial de las técnicas de diagnóstico por imagen en la investigación biomédica de la enfermedad de Chagas

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