3-Trifluoromethylquinoxaline N,N'-dioxides as anti-trypanosomatid agents. Identification of optimal anti-T. cruzi agents and mechanism of action studies.
J Med Chem
; 54(10): 3624-36, 2011 May 26.
Article
em En
| MEDLINE
| ID: mdl-21506600
For a fourth approach of quinoxaline N,N'-dioxides as anti-trypanosomatid agents against T. cruzi and Leishmania, we found extremely active derivatives. The present study allows us to state the correct requirements for obtaining optimal in vitro anti-T. cruzi activity. Derivatives possessing electron-withdrawing substituents in the 2-, 3-, 6-, and 7-positions were the most active compounds. With regard to these features and taking into account their mammal cytotoxicity, some trifluoromethylquinoxaline N,N'-dioxides have been proposed as candidates for further clinical studies. Consequently, mutagenicity and in vivo analyses were performed with the most promising derivatives. In addition, with regard to the mechanism of action studies, it was demonstrated that mitochondrial dehydrogenases are involved in the anti-T. cruzi activity of the most active derivatives.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinoxalinas
/
Óxidos N-Cíclicos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Uruguai
País de publicação:
Estados Unidos