Trypanocidal activity of the phenyl-substituted analogue of furamidine DB569 against Trypanosoma cruzi infection in vivo.
OBJECTIVE
Aromatic diamidines have been successfully used to combat a wide range of parasites that cause important human infections. One such compound is furamidine (DB75) and we recently reported that one of its analogues, an N-phenyl analogue (DB569), exhibits higher trypanocidal dose and time-dependent effects against different forms of Trypanosoma cruzi as compared with DB75. Our present aim was to investigate the efficacy of DB569 in a T. cruzi mouse model.


METHODS
The trypanocidal activity of the compound was evaluated by clinical, parasitological, histopathological and biochemical investigations.


RESULTS
Treatment with DB569 significantly reduced cardiac parasitism, partially increased the survival rates of mice and lowered the levels of alanine aminotransferase and creatinine indicating a protective role against renal and hepatic lesions caused by the parasite infection.


CONCLUSIONS
Altogether, the data support the potential effect of this class of compounds against T. cruzi and motivate the screening of new diamidines for efficacy against Chagas' disease.
de Souza
Elen M
EM
Lab. Biologia Celular, DUBC, Instituto Oswaldo Cruz FIOCRUZ, Rio de Janeiro, RJ, Brasil.
Oliveira
Gabriel M
GM
Boykin
David W
DW
Kumar
Arvind
A
Hu
Qiyue
Q
De Nazaré C Soeiro
Maria
M
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001550:Benzamidines / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D014355:Chagas Disease / Q000188:drug therapy*; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000469:parasitology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D013997:Time Factors; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
D001550:Benzamidines; C514550:DB569 compound; D014344:Trypanocidal Agents; C033286:furamidine; D000410:Alanine Transaminase; D003402:Creatine Kinase