Activity of dihydrofolate reductase inhibitors on the hepatic stages of Plasmodium yoelii yoelii in vitro.
The effects of the dihydrofolate reductase inhibitors proguanil and chlorproguanil, their active metabolites cycloguanil and chlorcycloguanil, and pyrimethamine, against the hepatic stages of Plasmodium yoelii yoellii were investigated in cultured BALB/c mouse hepatocytes. Proguanil was inactive at concentrations of 10(-8) M, whereas the other compounds were fully active at this and lower concentrations. Chlorcycloguanil was the most active compound and almost completely inhibited schizont development in concentrations as low as 10(-12) M.
Eriksson
B
B
Department of Infectious Diseases, Karolinska Institute, Roslagstull Hospital, Stockholm, Sweden.
Courtier
B
B
Bjŏrkman
A
A
Miltgen
F
F
Mazier
D
D
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005493:Folic Acid Antagonists; D008099:Liver / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000187:drug effects*; D002727:Proguanil / Q000031:analogs & derivatives / Q000494:pharmacology; D011739:Pyrimethamine / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology
D000962:Antimalarials; D005493:Folic Acid Antagonists; D014227:Triazines; C026009:cycloguanil; C007030:chlorproguanil; D002727:Proguanil; D011739:Pyrimethamine