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In vitro investigation of the efficacy of novel diamidines against Trypanosoma cruzi

Published online by Cambridge University Press:  15 April 2014

B. L. TIMM ,
P. B. DA SILVA ,
M. M. BATISTA ,
A. A. FARAHAT ,
A. KUMAR ,
D. W. BOYKIN  and
M. N. C. SOEIRO
B. L. TIMM
Affiliation:
Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21040-360, Brazil
P. B. DA SILVA
Affiliation:
Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21040-360, Brazil
M. M. BATISTA
Affiliation:
Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21040-360, Brazil
A. A. FARAHAT
Affiliation:
Department of Chemistry, Georgia State University, Atlanta, Georgia, USA Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
A. KUMAR
Affiliation:
Department of Chemistry, Georgia State University, Atlanta, Georgia, USA
D. W. BOYKIN
Affiliation:
Department of Chemistry, Georgia State University, Atlanta, Georgia, USA
M. N. C. SOEIRO*
Affiliation:
Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21040-360, Brazil
*
*Corresponding author: Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil. E-mail: soeiro@ioc.fiocruz.br
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Summary

Chagas’ disease is a neglected tropical disease caused by Trypanosoma cruzi and constitutes a serious public health problem for Latin America. Its unsatisfactory chemotherapy stimulates the search for novel antiparasitic compounds. Amidines and related compounds exhibit well-known activity towards different microbes including T. cruzi. In this vein, our present aim was to evaluate the biological effect of 10 novel structurally related amidines in vitro against bloodstream and intracellular forms of the parasite as well as their potential toxicity on cardiac cell cultures. Our results show that although active against the extracellular forms, with some of them like DB2247 being 6-fold more effective than benznidazole and displaying very low toxicity (>96 μm), none presented superior trypanocidal effect against intracellular forms as compared with the reference drug. These results may be due to differences in susceptibility profiles related to distinct uptake/extrusion mechanisms and cellular targets between bloodstream and amastigote forms. The present study adds to the knowledge base for the future design of novel amidines that may provide promising activity against T. cruzi.

Keywords

Chagas diseaseexperimental chemotherapyaromatic diamidines
Type
Research Article
Information
Parasitology , Volume 141 , Issue 10 , September 2014 , pp. 1272 - 1276
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Copyright
Copyright © Cambridge University Press 2014 

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