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Antiparasitic and anti-inflammatory activities of ß-lapachone-derived naphthoimidazoles in experimental acute Trypanosoma cruzi infection
- Source :
- Memórias do Instituto Oswaldo Cruz., Vol 115 (2020), Memórias do Instituto Oswaldo Cruz, Volume: 115, Article number: e190389, Published: 14 FEB 2020, Memórias do Instituto Oswaldo Cruz
- Publication Year :
- 2020
- Publisher :
- Instituto Oswaldo Cruz, Ministério da Saúde, 2020.
-
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.
- Subjects :
- Male
Microbiology (medical)
Chagas disease
Time Factors
medicine.drug_class
medicine.medical_treatment
Trypanosoma cruzi
030231 tropical medicine
RC955-962
Anti-Inflammatory Agents
Inflammation
heart
Pharmacology
Parasitemia
chemotherapy
Microbiology
Anti-inflammatory
Electrocardiography
Mice
03 medical and health sciences
0302 clinical medicine
In vivo
Arctic medicine. Tropical medicine
parasitic diseases
medicine
Animals
Chemotherapy
biology
business.industry
medicine.disease
biology.organism_classification
Trypanocidal Agents
In vitro
QR1-502
Disease Models, Animal
Nitroimidazoles
Benznidazole
Acute Disease
naphthoimidazoles
Original Article
medicine.symptom
business
cardiomyopathy
Naphthoquinones
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 16788060
- Volume :
- 115
- Database :
- OpenAIRE
- Journal :
- Memórias do Instituto Oswaldo Cruz.
- Accession number :
- edsair.doi.dedup.....41db080381e771f4be9efb476081f672