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4-Nitrobenzaldehyde thiosemicarbazone: a new compound derived from S-(-)-limonene that induces mitochondrial alterations in epimastigotes and trypomastigotes of Trypanosoma cruzi

Published online by Cambridge University Press:  25 February 2015

ELIZANDRA APARECIDA BRITTA ,
DÉBORA BOTURA SCARIOT ,
HUGO FALZIROLLI ,
CLEUZA CONCEIÇÃO DA SILVA ,
TÂNIA UEDA-NAKAMURA ,
BENEDITO PRADO DIAS FILHO ,
REDOUANE BORSALI  and
CELSO VATARU NAKAMURA
ELIZANDRA APARECIDA BRITTA
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, PR, Avenida Colombo, 5790, Jd. Universitário, Maringá, Paraná 87020-900, Brazil
DÉBORA BOTURA SCARIOT
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, PR, Avenida Colombo, 5790, Jd. Universitário, Maringá, Paraná 87020-900, Brazil
HUGO FALZIROLLI
Affiliation:
Departamento de Química, Universidade Estadual de Maringá, Maringá, PR, Avenida Colombo, 5790, Jd. Universitário, Maringá, Paraná 87020-900, Brazil
CLEUZA CONCEIÇÃO DA SILVA
Affiliation:
Departamento de Química, Universidade Estadual de Maringá, Maringá, PR, Avenida Colombo, 5790, Jd. Universitário, Maringá, Paraná 87020-900, Brazil
TÂNIA UEDA-NAKAMURA
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, PR, Avenida Colombo, 5790, Jd. Universitário, Maringá, Paraná 87020-900, Brazil
BENEDITO PRADO DIAS FILHO
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, PR, Avenida Colombo, 5790, Jd. Universitário, Maringá, Paraná 87020-900, Brazil
REDOUANE BORSALI
Affiliation:
Univ. Grenoble Alpes, CERMAV-CNRS UPR 5301, F-38000 Grenoble, France
CELSO VATARU NAKAMURA*
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, PR, Avenida Colombo, 5790, Jd. Universitário, Maringá, Paraná 87020-900, Brazil
*
*Corresponding author. Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, PR, Avenida Colombo, 5790, Jd. Universitário, Maringá, Paraná 87020-900, Brazil. E-mail: cvnakamura@uem.br
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Summary

Trypanosoma cruzi is the causative agent of Chagas’ disease, a parasitic disease that remains a serious health concern with unsatisfactory treatment. Drugs that are currently used to treat Chagas’ disease are partially effective in the acute phase but ineffective in the chronic phase of the disease. The aim of the present study was to evaluate the antitrypanosomal activity and morphological, ultrastructural and biochemical alterations induced by a new molecule, 4-nitrobenzaldehyde thiosemicarbazone (BZTS), derived from S-(-)-limonene against epimastigote, trypomastigote and intracellular amastigote forms of T. cruzi. BZTS inhibited the growth of epimastigotes (IC50 = 9·2 μm), intracellular amastigotes (IC50 = 3·23 μm) and inhibited the viability of trypomastigotes (EC50 = 1·43 μm). BZTS had a CC50 of 37·45 μm in LLCMK2 cells. BZTS induced rounding and distortion of the cell body and severely damaged parasite mitochondria, reflected by extensive swelling and disorganization in the inner mitochondrial membrane and the presence of concentric membrane structures inside the organelle. Cytoplasmic vacuolization, endoplasmic reticulum that surrounded organelles, the loss of mitochondrial membrane potential, and increased mitochondrial O2•ˉ production were also observed. Our results suggest that BZTS alters the ultrastructure and physiology of mitochondria, which could be closely related to parasite death.

Keywords

Trypanosoma cruziantitrypanosomal activity4-nitrobenzaldehyde thiosemicarbazonemitochondria alterationscell death
Type
Research Article
Information
Parasitology , Volume 142 , Issue 7 , June 2015 , pp. 978 - 988
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Copyright
Copyright © Cambridge University Press 2015 

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