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ABSTRACT: The aim of this study was to identify new compounds active againstPlasmodium falciparum based on our previous research carried out on 3-phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives. Twelve compounds weresynthesized and evaluated for antimalarial activity. Eight of them showed an IC50 less than 1 ÃŽÂ¼Magainst the 3D7 strain. Derivative 1 demonstrated high potency (IC50= 0.63 ÃŽÂ¼M) and goodselectivity (SI=10.35), thereby becoming a new lead-compound.