title: Antiplasmodial structure-activity relationship of 3-trifluoromethyl-2-arylcarbonylquinoxaline 1,4-di-N-oxide derivatives.
abstract: Derivatives of 3-trifluoromethyl-2-arylcarbonylquinoxaline 1,4-di-N-oxide (4b-g, 5b-g, 6a-g) were synthesized and evaluated for their capacity to inhibit the growth of chloroquine-resistant Plasmodium falciparum FCB1 strain in culture. Compound 7-chloro-2-(2-furylcarbonyl)-3-trifluoromethyl-1,4-quinoxaline di-N-oxide (5g) was the most active being almost 5 times more active than chloroquine. It was also 50 times more active against P. falciparum than toxic toward MCF7 cells. Structural characteristics for a quinoxaline to be active were defined: bioisosteric modification of phenyl group by 2-thienyl or 2-furyl subunits, R2 position must be free or occupied by a methyl group and R1 position must be free or occupied by Cl, CH3, OCH3 or CF3.
authors.affiliation: Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada, University of Navarra, Campus Universitario, 31080 Pamplona, Spain.
authors.forename: Adoración
authors.initials: A
authors.lastname: Marin
authors.forename: Lidia
authors.initials: L
authors.lastname: Moreira Lima
authors.forename: Beatriz
authors.initials: B
authors.lastname: Solano
authors.forename: Esther
authors.initials: E
authors.lastname: Vicente
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez Silanes
authors.forename: Séverine
authors.initials: S
authors.lastname: Maurel
authors.forename: Michel
authors.initials: M
authors.lastname: Sauvain
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
authors.forename: Eric
authors.initials: E
authors.lastname: Deharo
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects*; D011810:Quinoxalines / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: C527147:3-trifluoromethyl-2-arylcarbonylquinoxaline 1,4-di-N-oxide; D000962:Antimalarials; D011810:Quinoxalines