New polyamine drugs as more effective antichagas agents than benznidazole in both the acute and chronic phases

Martín‐Escolano, Rubén; Molina-Carreño, Daniel; Delgado‐Pinar, Estefanía; Martín‐Montes, Álvaro; Clares, M. Paz; Medina‐Carmona, Encarnación; Pitarch‐Jarque, Javier; Martín‐Escolano, Javier; Rosales, María J.; Garcı́a-España, Enrique; Sánchez‐Moreno, Manuel; Marı́n, Clotilde

doi:10.1016/j.ejmech.2018.12.034

Cited by 15 publications

(35 citation statements)

References 79 publications

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“…Figure 2B shows the reactivation of infection for each mice group compared to untreated (control) mice. As expected, BZN exhibited higher efficacy in chronic CD than in acute CD (reactivations of 81% and 68% in acute and chronic CD, respectively); it is widely known that BZN is more effective in chronic than in acute CD in mice models [38,42], probably because the parasitic load is low and limited to a few locations. Interestingly, compound 8 showed higher efficacy than BZN in both acute and chronic CD, with reactivations of 67% and 44%, respectively.…”

Section: In Vivo Biological Evaluationsupporting

confidence: 73%

“…Trypanocidal activity against amastigotes was determined according to the literature reported previously [ 42 ]. In short, culture derived trypomastigotes (obtained as previously described [ 56 ]) were used to infect 1 × 10 4 Vero cells·well −1 in 24-well microplates with rounded coverslips at a multiplicity of infection (MOI) ratio of 10:1 for 24 h. After that, non-phagocyted trypomastigotes were washed and the plates were treated by adding the tested compounds at a concentration range from 50 to 0.1 µM in 500 mL·well −1 at 37 °C in 95% humidified air and 5% CO 2 atmosphere.…”

Section: Methodsmentioning

confidence: 99%

“…2 × 10 6 Bloodstream trypomastigotes (BTs), obtained by cardiac puncture from infected BALB/c mice as previously described [ 56 ], were treated by adding the tested compounds at a concentration range from 50 to 0.1 µM in 96-well microplates (200 µL·well −1 ) at 37 °C. After 24 h of treatment, resazurin sodium salt (Sigma-Aldrich) was added to be incubated for further 4 h [ 42 ]. Finally, trypanocidal activity was determined following the same procedure as described to assess the trypanocidal activity in the epimastigotes.…”

Section: Methodsmentioning

confidence: 99%

Section: Screening Against Intracellular Amastigotes and Infected Cellsmentioning

confidence: 99%

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Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma cruzi Mitochondrion

et al. 2021

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Chagas disease is usually caused by tropical infection with the insect-transmitted protozoan Trypanosoma cruzi. Currently, Chagas disease is a major public health concern worldwide due to globalization, and there are no treatments neither vaccines because of the long-term nature of the disease and its complex pathology. Current treatments are limited to two obsolete drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Taking into account the urgent need for strict research efforts to find new therapies, here, we describe the in vitro and in vivo trypanocidal activity of a library of selected forty-eight selenocyanate and diselenide derivatives that exhibited leishmanicidal properties. The inclusion of selenium, an essential trace element, was due to the well-known extensive pharmacological activities for selenium compounds including parasitic diseases as T. cruzi. Here we present compound 8 as a potential compound that exhibits a better profile than benznidazole both in vitro and in vivo. It shows a fast-acting behaviour that could be attributed to its mode of action: it acts in a mitochondrion-dependent manner, causing cell death by bioenergetic collapse. This finding provides a step forward for the development of a new antichagasic agent.

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Section: In Vivo Biological Evaluationsupporting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Screening Against Intracellular Amastigotes and Infected Cellsmentioning

confidence: 99%

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Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma cruzi Mitochondrion

et al. 2021

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“…Nesa última, os níveis de parasitemia são oscilantes, sendo marcada por uma série de manifestações gastrintestinais e/ou cardíacas, resultando em comprometimento de funções vitais, que resulta em aumento do número de internações e óbitos. [3][4][5] Estimativas recentes apontam um quadro preocupante no cenário brasileiro, visto que o número de indivíduos infectados pelo T. cruzi nas cinco regiões do país é de aproximadamente 2 milhões. 6 A região Nordeste do Brasil, mais especificamente, é composta por nove estados: Alagoas, Bahia, Ceará, Maranhão, Paraíba, Pernambuco, Piauí, Rio Grande do Norte e Sergipe.…”

Section: IIIunclassified

Doença De Chagas: Perfil De Morbidade Hospitalar Na Região Do Nordeste Brasileiro

Silva¹,

Júnior²,

Dantas³

2019

Rev. Ciênc. Saúde Nova Esperança

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A Doença de Chagas (DC) é uma infecção parasitária que acomete milhões de indivíduos no mundo, principalmente, os que vivem em países marcados pela pobreza. Levando em conta a dimensão desta doença negligenciada. Assim, o presente estudo tem por objetivo avaliar variáveis associadas a morbidade hospitalar por DC na região Nordeste do Brasil. Para isso, foram utilizados os dados armazenados no Sistema de Informações Hospitalares do SUS (SIH/SUS), referente ao número de internações e de óbitos, taxa de mortalidade hospitalar, valor médio por internação e valor total das internações, regime, caráter de atendimento, sexo e cor/raça, considerando a população do Nordeste, no período de 2008 a 2018. Os dados obtidos apontaram que os anos de 2008 e 2011 foram, respectivamente, os anos de maior e menor registros de internações. No entanto, 2008 deteve a taxa de mortalidade hospitalar mais baixa. Considerando todo o período, foram gastos US$ 1.272.109,80 em internações, o que equivale a um valor médio por internação de US$ 675,20. A maior parte das internações foram realizadas no sistema público de saúde, além de serem de caráter de urgência. Também se verificou que o sexo masculino apresentou maiores registros em todas as variáveis quando comparados com o sexo feminino. Ademais, a cor parda foi predominante em relação às demais. Dessa maneira, pode-se perceber um alto investimento para tratamento de pessoas acometidas com doenças de chagas que vem reduzindo ao longo dos anos, associado também a redução do número de internações hospitalares, e aumento da taxa de mortalidade.

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Repositioning of leishmanicidal [1,2,3]Triazolo[1,5-a]pyridinium salts for Chagas disease treatment: Trypanosoma cruzi cell death involving mitochondrial membrane depolarisation and Fe-SOD inhibition

Martín‐Escolano

Ballesteros‐Garrido

et al. 2020

Parasitol Res

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New polyamine drugs as more effective antichagas agents than benznidazole in both the acute and chronic phases

Cited by 15 publications

References 79 publications

Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma cruzi Mitochondrion

Library of Selenocyanate and Diselenide Derivatives as In Vivo Antichagasic Compounds Targeting Trypanosoma cruzi Mitochondrion

Doença De Chagas: Perfil De Morbidade Hospitalar Na Região Do Nordeste Brasileiro

Repositioning of leishmanicidal [1,2,3]Triazolo[1,5-a]pyridinium salts for Chagas disease treatment: Trypanosoma cruzi cell death involving mitochondrial membrane depolarisation and Fe-SOD inhibition

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