In vitro activity of the enantiomers of N-desbutyl derivative of halofantrine.
The in vitro activity of the enantiomers of N-desbutylhalofantrine, the major human metabolite of halofantrine, was compared using the semi-microtest against the multidrug-resistant Plasmodium falciparum FCM 29/Cameroon clone. The mean 50% inhibitory concentration (IC50) values (+/- standard deviation) of the enantiomers were equivalent (2.07 +/- 0.41 and 1.70 +/- 0.33 nmol/L). The enantiomers of the metabolite of halofantrine, as well as those of the parent compound, have the same antimalarial activity. Since (+)-halofantrine and enantiomer-1 of the metabolite attain higher plasma concentrations in man, our study suggests that these enantiomers may be more active in vivo.
Basco
L K
LK
Department of Parasitology, Hôpital Bichat-Claude Bernard, Paris, France.
Peytavin
G
G
Gimenez
F
F
Genissel
B
B
Farinotti
R
R
Le Bras
J
J
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance; D006801:Humans; D066298:In Vitro Techniques; D010616:Phenanthrenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D013237:Stereoisomerism
D000962:Antimalarials; D010616:Phenanthrenes; C044961:1,3-dichloro-6-trifluoromethyl-9-phenanthryl-3-(n-butyl)aminopropanol