Antimalarial asexual stage-specific and gametocytocidal activities of HIV protease inhibitors.
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.
Peatey
Christopher L
CL
Queensland Institute of Medical Research, 300 Herston Rd., Herston, Queensland, Australia.
Andrews
Katherine T
KT
Eickel
Nina
N
MacDonald
Timothy
T
Butterworth
Alice S
AS
Trenholme
Katharine R
KR
Gardiner
Donald L
DL
McCarthy
James S
JS
Skinner-Adams
Tina S
TS
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
D000962:Antimalarials; D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D000069454:Darunavir; C107201:tipranavir