Antimalarial activity of optical isomers of quinacrine dihydrochloride against chloroquine-sensitive and -resistant Plasmodium falciparum in vitro.
Both enantiomers of quinacrine and the racemic form of the drug showed equal activity in vitro against chloroquine-sensitive and -resistant strains of Plasmodium falciparum, without detectable stereoselectivity. This contrasts with observations on chloroquine, where a similar lack of stereoselectivity in vitro is accompanied by a 10-fold loss of activity against the resistant strain. The observed in vivo differences reported for the enantiomers of chloroquine and the observations on the optically active metabolites of chloroquine and quinacrine may therefore be ascribed to a difference in the pharmacokinetics of their enantiomers.
Webster
R V
RV
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143-0446.
Craig
J C
JC
Shyamala
V
V
Kirby
G C
GC
Warhurst
D C
DC
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D011796:Quinacrine / Q000493:pharmacokinetics / Q000494:pharmacology*; D013237:Stereoisomerism
D000962:Antimalarials; D002738:Chloroquine; D011796:Quinacrine