Antiplasmodial structure-activity relationship of 3-trifluoromethyl-2-arylcarbonylquinoxaline 1,4-di-N-oxide derivatives.
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.
Marin
Adoración
A
Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada, University of Navarra, Campus Universitario, 31080 Pamplona, Spain.
Moreira Lima
Lidia
L
Solano
Beatriz
B
Vicente
Esther
E
Pérez Silanes
Silvia
S
Maurel
Séverine
S
Sauvain
Michel
M
Aldana
Ignacio
I
Monge
Antonio
A
Deharo
Eric
E
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
C527147:3-trifluoromethyl-2-arylcarbonylquinoxaline 1,4-di-N-oxide; D000962:Antimalarials; D011810:Quinoxalines