title: Antimalarial asexual stage-specific and gametocytocidal activities of HIV protease inhibitors.
abstract: The stage-specific antimalarial activities of a panel of antiretroviral protease inhibitors (PIs), including two nonpeptidic PIs (tipranavir and darunavir), were tested in vitro against Plasmodium falciparum. While darunavir demonstrated limited antimalarial activity (effective concentration [EC(50)], >50 microM), tipranavir was active at clinically relevant concentrations (EC(50), 12 to 21 microM). Saquinavir, lopinavir, and tipranavir preferentially inhibited the growth of mature asexual-stage parasites (24 h postinvasion). While all of the PIs tested inhibited gametocytogenesis, tipranavir was the only one to exhibit gametocytocidal activity.
authors.affiliation: Queensland Institute of Medical Research, 300 Herston Rd., Herston, Queensland, Australia.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Peatey
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Andrews
authors.forename: Nina
authors.initials: N
authors.lastname: Eickel
authors.forename: Timothy
authors.initials: T
authors.lastname: MacDonald
authors.forename: Alice S
authors.initials: AS
authors.lastname: Butterworth
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Trenholme
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gardiner
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
authors.forename: Tina S
authors.initials: TS
authors.lastname: Skinner-Adams
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D000069454:Darunavir; D004912:Erythrocytes / Q000469:parasitology; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D008018:Life Cycle Stages; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development*; D011725:Pyridines / Q000494:pharmacology; D011753:Pyrones / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D000069454:Darunavir; C107201:tipranavir