Antimalarial activity of HIV-1 protease inhibitor in chromone series

• HIV-1 protease inhibitor in chromone series was tested for antimalarial activity.
• Chromone 15 was found to be the most potent antimalarial with IC50 = 0.95 μM.
• Docking study of chromone compounds against plasmepsin II was performed.
• Chromone 15 also showed the strongest binding energy against plasmepsin II.
• Chromone series has the potential to be a new class of antimalarial drug.

Increasing parasite resistance to nearly all available antimalarial drugs becomes a serious problem to human health and necessitates the need to continue the search for new effective drugs. Recent studies have shown that clinically utilized HIV-1 protease (HIV-1 PR) inhibitors can inhibit the in vitro and in vivo growth of Plasmodium falciparum. In this study, a series of chromone derivatives possessing HIV-1 PR inhibitory activity has been tested for antimalarial activity against P. falciparum (K1 multi-drug resistant strain). Chromone 15, the potent HIV-1 PR inhibitor (IC50 = 0.65 μM), was found to be the most potent antimalarial compound with IC50 = 0.95 μM while primaquine and tafenoquine showed IC50 = 2.41 and 1.95 μM, respectively. Molecular docking study of chromone compounds against plasmepsin II, an aspartic protease enzyme important in hemoglobin degradation, revealed that chromone 15 exhibited the higher binding affinity (binding energy = −13.24 kcal/mol) than the known PM II inhibitors. Thus, HIV-1 PR inhibitor in chromone series has the potential to be a new class of antimalarial agent.

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