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The efficacy of novel arylimidamides against Trypanosoma cruzi in vitro

Published online by Cambridge University Press:  09 September 2011

CRISTIANE FRANÇA DA SILVA ,
ANISSA DALIRY ,
PATRÍCIA BERNARDINO DA SILVA ,
SENOL AKAY ,
MOLOY BANERJEE ,
ABDELBASSET A. FARAHAT ,
MARY K. FISHER ,
LAIXING HU ,
ARVIND KUMAR  and
ZONGYING LIU
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CRISTIANE FRANÇA DA SILVA
Affiliation:
Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365. Manguinhos, Rio de Janeiro, RJ, Brazil
ANISSA DALIRY
Affiliation:
Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365. Manguinhos, Rio de Janeiro, RJ, Brazil
PATRÍCIA BERNARDINO DA SILVA
Affiliation:
Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365. Manguinhos, Rio de Janeiro, RJ, Brazil
SENOL AKAY
Affiliation:
Department of Chemistry, Augusta State University, Augusta, Georgia, USA
MOLOY BANERJEE
Affiliation:
Department of Chemistry, Augusta State University, Augusta, Georgia, USA
ABDELBASSET A. FARAHAT
Affiliation:
Department of Chemistry, Augusta State University, Augusta, Georgia, USA
MARY K. FISHER
Affiliation:
Department of Chemistry and Physics, Augusta State University, Augusta, Georgia, USA
LAIXING HU
Affiliation:
Department of Chemistry, Augusta State University, Augusta, Georgia, USA
ARVIND KUMAR
Affiliation:
Department of Chemistry, Augusta State University, Augusta, Georgia, USA
ZONGYING LIU
Affiliation:
Department of Chemistry, Augusta State University, Augusta, Georgia, USA
CHAD E. STEPHENS
Affiliation:
Department of Chemistry and Physics, Augusta State University, Augusta, Georgia, USA
DAVID W. BOYKIN
Affiliation:
Department of Chemistry, Augusta State University, Augusta, Georgia, USA
MARIA DE NAZARÉ CORREIA SOEIRO*
Affiliation:
Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365. Manguinhos, Rio de Janeiro, RJ, Brazil
*
*Corresponding author: Laboratório de Biologia Celular, Maria de Nazaré Correia Soeiro, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, Brazil. Tel: +055 21 25621368. Fax: +055 21 2562-1432. E-mail: [email protected]
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Summary

The present study aimed to determine the in vitro biological efficacy and selectivity of 7 novel AIAs upon bloodstream trypomastigotes and intracellular amastigotes of Trypanosoma cruzi. The biological activity of these aromatic compounds was assayed for 48 and 24 h against intracellular parasites and bloodstream forms of T. cruzi (Y strain), respectively. Additional assays were also performed to determine their potential use in blood banks by treating the bloodstream parasites with the compounds diluted in mouse blood for 24 h at 4°C. Toxicity against mammalian cells was evaluated using primary cultures of cardiac cells incubated for 24 and 48 h with the AIAs and then cellular death rates were determined by MTT colorimetric assays. Our data demonstrated the outstanding trypanocidal effect of AIAs against T. cruzi, especially DB1853, DB1862, DB1867 and DB1868, giving IC50 values ranging between 16 and 70 nanomolar against both parasite forms. All AIAs presented superior efficacy to benznidazole and some, such as DB1868, also demonstrated promising activity as a candidate agent for blood prophylaxis. The excellent anti-trypanosomal efficacy of these novel AIAs against T. cruzi stimulates further in vivo studies and justifies the screening of new analogues with the goal of establishing a useful alternative therapy for Chagas disease.

Keywords

Trypanosoma cruziChagas diseasechemotherapyarylimidamides
Type
Research Article
Information
Parasitology , Volume 138 , Issue 14 , December 2011 , pp. 1863 - 1869
Copyright
Copyright © Cambridge University Press 2011

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