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3-Trifluoromethylquinoxaline N,N'-dioxides as anti-trypanosomatid agents. Identification of optimal anti-T. cruzi agents and mechanism of action studies.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Benitez D,Cabrera M,Hernández P,Boiani L,Lavaggi ML,Di Maio R,Yaluff G,Serna E,Torres S,Ferreira ME,Vera de Bilbao N,Torres E,Pérez-Silanes S,Solano B,Moreno E,Aldana I,López de Ceráin A,Cerecetto H,González M,Monge

doi

10.1021/jm2002469

subject

Has Abstract

pub_date

2011-05-26 00:00:00

pages

3624-36

issue

10

eissn

0022-2623

issn

1520-4804

journal_volume

54

pub_type

杂志文章

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