title: Anti-Trypanosoma cruzi and anti-leishmanial activity by quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives.
abstract: In this work, a novel series of ethyl and methyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives were evaluated in vitro on Trypanosoma cruzi trypomastigotes and Leishmania mexicana promastigotes, and cytotoxicity activity in murine macrophages was tested. In silico molecular docking simulations of trypanothione reductase were also done. Three compounds of 33 quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives showed better anti-T. cruzi activity than nifurtimox and beznidazole; two compounds had better anti-leishmanial activity that amphotericin-B, and two compounds showed better activity against both parasites than reference drugs. Compounds M2, M7, M8 and E5, showed low cytotoxic activity on the host cell. The in silico studies suggest that compound M2 is a potential trypanothione reductase inhibitor.
authors.affiliation: Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, s/n, 11340, D.F., Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Villalobos-Rocha
authors.forename: Luvia
authors.initials: L
authors.lastname: Sánchez-Torres
authors.forename: Benjamín
authors.initials: B
authors.lastname: Nogueda-Torres
authors.forename: Aldo
authors.initials: A
authors.lastname: Segura-Cabrera
authors.forename: Carlos A
authors.initials: CA
authors.lastname: García-Pérez
authors.forename: Virgilio
authors.initials: V
authors.lastname: Bocanegra-García
authors.forename: Isidro
authors.initials: I
authors.lastname: Palos
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
authors.forename: Gildardo
authors.initials: G
authors.lastname: Rivera
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D007894:Leishmania mexicana / Q000187:drug effects*; D008264:Macrophages; D051379:Mice; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D011810:Quinoxalines