title: Antimalarial activity of HIV-1 protease inhibitor in chromone series.
abstract: 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=0.65μM), was found to be the most potent antimalarial compound with IC50=0.95μM while primaquine and tafenoquine showed IC50=2.41 and 1.95μM, 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=-13.24kcal/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.
authors.affiliation: Chulabhorn Research Institute, Bangkok, Thailand.
authors.forename: Pradith
authors.initials: P
authors.lastname: Lerdsirisuk
authors.affiliation: Center of Excellence for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Road, Bangkok 10400, Thailand.
authors.forename: Chirattikan
authors.initials: C
authors.lastname: Maicheen
authors.affiliation: Center of Excellence for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Road, Bangkok 10400, Thailand. Electronic address: jiraporn.ung@mahidol.ac.th.
authors.forename: Jiraporn
authors.initials: J
authors.lastname: Ungwitayatorn
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002867:Chromones / Q000737:chemistry* / Q000494:pharmacology*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D062105:Molecular Docking Simulation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000962:Antimalarials; D002867:Chromones; D017320:HIV Protease Inhibitors; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II
keywords: Antimalarial activity; Chromone series; Docking; Plasmepsin II