Molecular Docking Study of Chromone Derivatives as Dual Inhibitor Against Plasmepsin II and Falcipain-2

Abstract

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.