Activity of benflumetol and its enantiomers in fresh isolates of Plasmodium falciparum from East Africa

Abstract

Benflumetol, a novel antimalarial compound belonging to the fluorenes (2,3-benzindenes), has high blood schizontocidal activity, in vitro and in vivo, against mammalian plasmodia, including chloroquine-resistant Plasmodium falciparum. Due to its molecular structure benflumetol occurs in the dextrorotatory and the laevorotatory form. Normal synthesis yields the racemate of both enantiomers. Enantiomers of some antimalarial drugs possess different specific activity. It was therefore of interest to compare the response of P. falciparum to the enantiomers and the racemate of benflumetol in a variety of fresh, natural isolates. Measuring the concentration-specific inhibition of schizont maturation, the parallel investigation of 29 isolates produced no evidence of substantial activity differences between (+)-benflumetol, (-)-benflumetol and racemic benflumetol, the mean EC-50 values being 8.87, 9.71 and 12.44 nmol/l blood-medium-mixture, respectively. Copyright (C) 1998 Elsevier Science B.V.