title: 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.
authors.affiliation: Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, 11400 Montevideo, Uruguay.
authors.forename: Diego
authors.initials: D
authors.lastname: Benitez
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cabrera
authors.forename: Paola
authors.initials: P
authors.lastname: Hernández
authors.forename: Lucía
authors.initials: L
authors.lastname: Boiani
authors.forename: María L
authors.initials: ML
authors.lastname: Lavaggi
authors.forename: Rossanna
authors.initials: R
authors.lastname: Di Maio
authors.forename: Gloria
authors.initials: G
authors.lastname: Yaluff
authors.forename: Elva
authors.initials: E
authors.lastname: Serna
authors.forename: Susana
authors.initials: S
authors.lastname: Torres
authors.forename: María E
authors.initials: ME
authors.lastname: Ferreira
authors.forename: Ninfa
authors.initials: N
authors.lastname: Vera de Bilbao
authors.forename: Enrique
authors.initials: E
authors.lastname: Torres
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez-Silanes
authors.forename: Beatriz
authors.initials: B
authors.lastname: Solano
authors.forename: Elsa
authors.initials: E
authors.lastname: Moreno
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
authors.forename: Adela
authors.initials: A
authors.lastname: López de Ceráin
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003497:Cyclic N-Oxides / Q000737:chemistry*; D015195:Drug Design; D004583:Electrons; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D009152:Mutagenicity Tests; D018512:Parasitemia / Q000188:drug therapy; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018675:Toxicity Tests; D014344:Trypanocidal Agents / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000378:metabolism
chemical_list: D003497:Cyclic N-Oxides; D011810:Quinoxalines; D014344:Trypanocidal Agents