Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents.
Bioorg Med Chem
; 18(22): 7826-35, 2010 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-20961766
ABSTRACT
In previous studies, we identified promising anti-Trypanosoma cruzi cruzain inhibitors based on thiazolylhydrazones. To optimize this series, a number of medicinal chemistry directions were explored and new thiazolylhydrazones and thiosemicarbazones were thus synthesized. Potent cruzain inhibitors were identified, such as thiazolylhydrazones 3b and 3j, which exhibited IC(50) of 200-400nM. Furthermore, molecular docking studies showed concordance with experimentally derived structure-activity relationships (SAR) data. In the course of this work, lead compounds exhibiting in vitro activity against both the epimastigote and trypomastigote forms of T. cruzi were identified and in vivo general toxicity analysis was subsequently performed. Novel SAR were documented, including the importance of the thiocarbonyl carbon attached to the thiazolyl ring and the direct comparison between thiosemicarbazones and thiazolylhydrazones.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triazóis
/
Tripanossomicidas
/
Hidrazonas
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article