Identification of a new amide-containing thiazole as a drug candidate for treatment of Chagas' disease.
Antimicrob Agents Chemother
; 59(3): 1398-404, 2015 Mar.
Article
in En
| MEDLINE
| ID: mdl-25512408
ABSTRACT
Although the parasitic infection Chagas' disease was described over 100 years ago, even now there are not suitable drugs. The available drugs nifurtimox and benznidazole have limited efficacies and tolerances, with proven mutagenic effects. Attempting to find appropriate drugs to deal with this problem, here we report on the development and pharmacological characterization of new amide-containing thiazoles. In the present study, we evaluated the in vitro and in vivo effects of new candidates against Trypanosoma cruzi, the etiological agent of Chagas' disease. The lead amide-containing thiazole derivative had potent in vitro activity, an absence of both in vitro mutagenic and in vivo clastogenic effects, and excellent in vitro selectivity and in vivo tolerance. The compound suppressed parasitemia in mice, modifying the anti-T. cruzi antibodies like the reference drug, benznidazole, and displayed the lowest mortality among the tested drugs. The present evidence suggests that this compound is a promising anti-T. cruzi agent surpassing the lead optimization stage in drug development and leading to a candidate for preclinical study.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiazoles
/
Trypanocidal Agents
/
Chagas Disease
/
Amides
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
Antimicrob Agents Chemother
Year:
2015
Document type:
Article
Affiliation country:
Uruguay