Antimalarial effects of vinyl sulfone cysteine proteinase inhibitors.
We evaluated the antimalarial effects of vinyl sulfone cysteine proteinase inhibitors. A number of vinyl sulfones strongly inhibited falcipain, a Plasmodium falciparum cysteine proteinase that is a critical hemoglobinase. In studies of cultured parasites, nanomolar concentrations of three vinyl sulfones inhibited parasite hemoglobin degradation, metabolic activity, and development. The antimalarial effects correlated with the inhibition of falcipain. Our results suggest that vinyl sulfones or related cysteine proteinase inhibitors may have promise as antimalarial agents.
Rosenthal
P J
PJ
Department of Medicine, San Francisco General Hospital, University of California 94143, USA. rosnthl@itsa.ucsf.edu
Olson
J E
JE
Lee
G K
GK
Palmer
J T
JT
Klaus
J L
JL
Rasnick
D
D
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology*
D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D006454:Hemoglobins; D013450:Sulfones; C009873:divinyl sulfone; D003546:Cysteine Endopeptidases; C099607:falcipain