Synthesis of aminoquinoline-based aminoalcohols and oxazolidinones and their antiplasmodial activity

Novel aminoquinoline β-aminoalcohol and oxazolidinone derivatives were designed, synthesized, and evaluated for in vitro antiplasmodial activity against a chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. A few β-aminoalcohol derivatives were more potent than chloroquine against chloroquine-sensetive Plasmodiums. The potency of these derivatives decreased against chloroquine-resistant species in all cases (higher resistance indices), suggesting a possible cross-resistance between this group of compounds and chloroquine which could be due to their structural similarity. Although changing β-aminoalcohols to their oxazolidinone counterparts decreased the potency in all the cases, the compounds were still active and the resistance indices for these compounds improved significantly in comparison with those of β-aminoalcohols. This may indicate the absence of cross-resistance between these new derivatives and chloroquine.