Experimental Parasitology 2008-01-01

Antiplasmodial structure-activity relationship of 3-trifluoromethyl-2-arylcarbonylquinoxaline 1,4-di-N-oxide derivatives.

Adoración Marin, Lidia Moreira Lima, Beatriz Solano, Esther Vicente, Silvia Pérez Silanes, Séverine Maurel, Michel Sauvain, Ignacio Aldana, Antonio Monge, Eric Deharo

Index: Exp. Parasitol. 118(1) , 25-31, (2008)

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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.