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Antimicrob Agents Chemother. 2015 Mar;59(3):1398-404. doi: 10.1128/AAC.03814-14. Epub 2014 Dec 15.

Identification of a new amide-containing thiazole as a drug candidate for treatment of Chagas' disease.

Author information

1
Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
2
Laboratorio de Experimentación Animal, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
3
Centro de Investigaciones de Enfermedades Tropicales, Departamento de Ciencias Básicas, Universidad Industrial de Santander, Bucaramanga, Colombia.
4
Departamento de Medicina Tropical, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción, Paraguay.
5
Departamento de Anatomía Patológica, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción, Paraguay.
6
Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay hcerecetto@cin.edu.uy megonzal@fq.edu.uy.

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.

PMID:
25512408
PMCID:
PMC4325761
DOI:
10.1128/AAC.03814-14
[Indexed for MEDLINE]
Free PMC Article

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