Malaria remains a major problem to human health and necessitates the need to continue the
search for new effective drugs. In this study, a series of chromone compounds with potent antimalarial
activity have been subjected to docking simulation study in order to preliminary evaluate the potential
as dual inhibitor against plasmepsin II (PM II) and falcipain-2 (FP-2). The results revealed that
compound 45 exhibited the best binding affinity (binding energy = -9.03 kcal/mol) to PM II and
showed high binding affinity to FP-2 (binding energy = -7.43 kcal/mol). Compound 47 showed the
strongest binding affinity (binding energy = -8.00 kcal/mol) against FP-2 and high binding with PM
II (binding energy = -6.73 kcal/mol). Both compounds showed more tightly binding than the known
dual PM II and FP-2 inhibitors, i.e., fisetin (binding energy = -6.53 and -4.97 kcal/mol against PM II
and FP-2, respectively) and myricetin (binding energy = -5.51 and -4.78 kcal/mol against PM II and
FP-2, respectively). Thus, chromone series have the potential to be a new class of antimalarial drug
with dual PM II and FP-2 inhibitory activity.
Keywords
molecular docking, chromone derivatives, plasmepsin II, falcipain-2, dual inhibitor.