Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection.

Autor:	Cascabulho CM; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Rio de Janeiro, RJ, Brasil., Meuser-Batista M; Fundação Oswaldo Cruz-Fiocruz, Instituto Fernandes Figueira, Departamento de Anatomia Patológica e Citopatologia, Laboratório de Patologia Molecular, Rio de Janeiro, RJ, Brasil., Moura KCG; Universidade Federal do Rio de Janeiro, Instituto de Pesquisa em Produtos Naturais, Rio de Janeiro, RJ, Brasil., Pinto MDC; Universidade Federal do Rio de Janeiro, Instituto de Pesquisa em Produtos Naturais, Rio de Janeiro, RJ, Brasil., Duque TLA; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil., Demarque KC; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil., Guimarães ACR; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Genômica Funcional e Bioinformática, Rio de Janeiro, RJ, Brasil., Manso PPA; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Patologia, Rio de Janeiro, RJ, Brasil., Pelajo-Machado M; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Patologia, Rio de Janeiro, RJ, Brasil., Oliveira GM; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil., Castro SL; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil., Menna-Barreto RF; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Celular, Rio de Janeiro, RJ, Brasil.
Jazyk:	angličtina
Zdroj:	Memorias do Instituto Oswaldo Cruz [Mem Inst Oswaldo Cruz] 2020 Feb 14; Vol. 115, pp. e190389. Date of Electronic Publication: 2020 Feb 14 (Print Publication: 2020).
DOI:	10.1590/0074-02760190389
Abstrakt:	Background: Chagas disease, which is caused by the protozoan Trypanosoma cruzi, is endemic to Latin America and mainly affects low-income populations. Chemotherapy is based on two nitrocompounds, but their reduced efficacy encourages the continuous search for alternative drugs. Our group has characterised the trypanocidal effect of naphthoquinones and their derivatives, with naphthoimidazoles derived from β-lapachone (N1, N2 and N3) being the most active in vitro. Objectives: In the present work, the effects of N1, N2 and N3 on acutely infected mice were investigated. Methods: in vivo activity of the compounds was assessed by parasitological, biochemical, histopathological, immunophenotypical, electrocardiographic (ECG) and behavioral analyses. Findings: Naphthoimidazoles led to a decrease in parasitaemia (8 dpi) by reducing the number of bloodstream trypomastigotes by 25-50% but not by reducing mortality. N1 protected mice from heart injury (15 dpi) by decreasing inflammation. Bradycardia was also partially reversed after treatment with N1 and N2. Furthermore, the three compounds did not reverse hepatic and renal lesions or promote the improvement of other evaluated parameters. Main Conclusion: N1 showed moderate trypanocidal and promising immunomodulatory activities, and its use in combination with benznidazole and/or anti-arrhythmic drugs as well as the efficacy of its alternative formulations must be investigated in the near future.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu