In vitro activities of the biguanide PS-15 and its metabolite, WR99210, against cycloguanil-resistant Plasmodium falciparum isolates from Thailand.
The in vitro activities of the new biguanide PS-15 and its putative active metabolite, WR99210, were determined against seven different isolates or clones of Plasmodium falciparum. The mean 50% inhibitory concentrations of PS-15 and WR99210 were 1,015 and 0.06 ng/ml, respectively. WR99210 was up to 363 times more potent than cycloguanil, the active metabolite of proguanil, against cycloguanil-resistant parasites. The pronounced activity of WR99210 against multidrug-resistant P. falciparum indicates that further studies are required to determine the value of the prodrug, PS-15, as an antimalarial agent.
Edstein
M D
MD
Australian Army Malaria Institute, Brisbane.
Bahr
S
S
Kotecka
B
B
Shanks
G D
GD
Rieckmann
K H
KH
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D008288:Malaria / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011355:Prodrugs / Q000494:pharmacology*; D002727:Proguanil / Q000031:analogs & derivatives* / Q000494:pharmacology; D012453:Saimiri; D013785:Thailand; D014227:Triazines / Q000494:pharmacology*
D000962:Antimalarials; D005493:Folic Acid Antagonists; D011355:Prodrugs; D014227:Triazines; C082651:PS 15; C026009:cycloguanil; D002727:Proguanil