Kojic acid derived hydroxypyridinone-chloroquine hybrids: synthesis, crystal structure, antiplasmodial activity and ß-haematin inhibition.

ABSTRACT

Aminochloroquinoline-kojic acid hybrids were synthesized and evaluated for ß-haematin inhibition and antiplasmodial activity against drug resistant (K1) and sensitive (3D7) strains of Plasmodium falciparum. Compound 7j was the most potent compound in both strains (IC50(3D7)=0.004 µM; IC50(K1)=0.03 µM) and had the best ß-haematin inhibition activity (0.07 IC50 equiv vs 1.91 IC50 equiv for chloroquine). One compound 8c was found to be equipotent in both strains (IC50=0.04 µM).