Antiparasitic and Anti-inflammatory Activities of ß-lapachone-derived Naphthoimidazoles in Experimental Acute Trypanosoma Cruzi Infection

Overview

Journal Mem Inst Oswaldo Cruz

Specialties Parasitology
Tropical Medicine

Date 2020 Feb 20

PMID 32074167

Citations 3

Authors

Cynthia M Cascabulho

Marcelo Meuser-Batista

Kelly Cristina G de Moura

Maria do Carmo Pinto

Thabata Lopes Alberto Duque

Kelly C Demarque

Ana Carolina Ramos Guimaraes

Pedro Paulo de Abreu Manso

Marcelo Pelajo-Machado

Gabriel M Oliveira

Solange L de Castro

Rubem Fs Menna-Barreto

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The evaluation of antichagasic and -SARS-CoV-2 potential of inclusion complexes of β- and methyl-β-cyclodextrin with naphthoquinone.

Oliveira V, Silva C, de Freitas Oliveira J, de Sousa da Silva M, Ferreira P, da Siva F J Drug Deliv Sci Technol. 2023; 81:104229.

PMID: 36776572 PMC: 9905044. DOI: 10.1016/j.jddst.2023.104229.

Experimental Combination Therapy with Amiodarone and Low-Dose Benznidazole in a Mouse Model of Trypanosoma cruzi Acute Infection.

Barbosa J, Pedra Rezende Y, Melo T, de Oliveira G, Cascabulho C, da Silva Pereira E Microbiol Spectr. 2022; 10(1):e0185221.

PMID: 35138142 PMC: 8826820. DOI: 10.1128/spectrum.01852-21.

Characterization and trypanocidal activity of a β-lapachone-containing drug carrier.

Barbosa J, Nicoletti C, da Silva P, Melo T, Futuro D, Ferreira V PLoS One. 2021; 16(3):e0246811.

PMID: 33661933 PMC: 7932091. DOI: 10.1371/journal.pone.0246811.

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