Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection
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.
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2020
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oai:scielo:S0074-027620200001003012020-02-11Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infectionCascabulho,Cynthia MMeuser-Batista,MarceloMoura,Kelly Cristina G dePinto,Maria do CarmoDuque,Thabata Lopes AlbertoDemarque,Kelly CGuimarães,Ana Carolina RamosManso,Pedro Paulo de AbreuPelajo-Machado,MarceloOliveira,Gabriel MCastro,Solange L DeMenna-Barreto,Rubem FS Trypanosoma cruzi Chagas disease chemotherapy naphthoimidazoles heart cardiomyopathy 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.info:eu-repo/semantics/openAccessInstituto Oswaldo Cruz, Ministério da SaúdeMemórias do Instituto Oswaldo Cruz v.115 20202020-01-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762020000100301en10.1590/0074-02760190389 |
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Cascabulho,Cynthia M Meuser-Batista,Marcelo Moura,Kelly Cristina G de Pinto,Maria do Carmo Duque,Thabata Lopes Alberto Demarque,Kelly C Guimarães,Ana Carolina Ramos Manso,Pedro Paulo de Abreu Pelajo-Machado,Marcelo Oliveira,Gabriel M Castro,Solange L De Menna-Barreto,Rubem FS |
spellingShingle |
Cascabulho,Cynthia M Meuser-Batista,Marcelo Moura,Kelly Cristina G de Pinto,Maria do Carmo Duque,Thabata Lopes Alberto Demarque,Kelly C Guimarães,Ana Carolina Ramos Manso,Pedro Paulo de Abreu Pelajo-Machado,Marcelo Oliveira,Gabriel M Castro,Solange L De Menna-Barreto,Rubem FS Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection |
author_facet |
Cascabulho,Cynthia M Meuser-Batista,Marcelo Moura,Kelly Cristina G de Pinto,Maria do Carmo Duque,Thabata Lopes Alberto Demarque,Kelly C Guimarães,Ana Carolina Ramos Manso,Pedro Paulo de Abreu Pelajo-Machado,Marcelo Oliveira,Gabriel M Castro,Solange L De Menna-Barreto,Rubem FS |
author_sort |
Cascabulho,Cynthia M |
title |
Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection |
title_short |
Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection |
title_full |
Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection |
title_fullStr |
Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection |
title_full_unstemmed |
Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection |
title_sort |
antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute trypanosoma cruzi infection |
description |
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. |
publisher |
Instituto Oswaldo Cruz, Ministério da Saúde |
publishDate |
2020 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762020000100301 |
work_keys_str_mv |
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