Kojic acid derived hydroxypyridinone–chloroquine hybrids: Synthesis, crystal structure, antiplasmodial activity and b-haematin inhibition

Abstract

Aminochloroquinoline–kojic acid hybrids were synthesized and evaluated for b-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 lM; IC50 K1 = 0.03 lM) and had the best b-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 lM).