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

Article abstract of DOI:10.1016/j.bmcl.2014.06.012

Aminochloroquinoline-kojic acid hybrids were synthesized and evaluated for β-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 β-haematin inhibition activity (0.07 IC₅₀ equiv vs 1.91 IC ₅₀ equiv for chloroquine). One compound 8c was found to be equipotent in both strains (IC₅₀ = 0.04 μM).