Novel oxazine skeletons as potential antiplasmodial active ingredients: Synthesis, in vitro and in vivo biology of some oxazine entities produced via cyclization of novel chalcone intermediates

Abstract

A novel series of 6-(2-chloroquinolin-3-yl)-4-substituted-phenyl-6H-1,3- oxazin-2-amines were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive (MRC-02) as well as chloroquine resistant (RKL9) strains of Plasmodium falciparum. The activity tested was at nanomolar concentration. β-Hematin formation inhibition activity (BHIA 50) of oxazines were determined and correlated with antimalarial activity. A reasonably good correlation (r=0.49 and 0.51, respectively) was observed between antimalarial activity (IC 50) and BHIA 50. This suggests that antimalarial mode of action of these compounds seems to be similar to that of chloroquine and involves the inhibition of hemozoin formation. Some of the compounds were showing better antimalarial activity than chloroquine against resistant strain of P. falciparum and were also found to be active in the in vivo experiment. © 2011 Informa UK, Ltd.