Desbutyl-benflumetol, a novel antimalarial compound: In vitro activity in fresh isolates of Plasmodium falciparum from Thailand

Desbutyl-benflumetol (DBB) is a novel antimalarial compound closely related to benflumetol (lumefantrine), of which it is a putative metabolite. The i n vitro response of Plasmodium falciparum Mae Hong Son and Mae Set, in nort hwest Thailand, in 1997 and 1998. In total, 155 fresh isolates were success fully tested using the World Health Organization standard in vitro microtes t system (Mark II). The mean 50% effective concentration (EC50) and 90% eff ective concentration of DBB were 6.36 and 31.09 nmol/liter, respectively. T he comparison of the activity of DBB and benflumetol yielded a highly signi ficant potency ratio of 4.52, corresponding to a more than four times highe r efficacy of DBB. A considerable potency difference was found between isol ates from Mae Hong Son and those from Mae Set, reflecting lesser sensitivit y in the area with marked resistance to mefloquine and quinine. This observ ation is also supported by a highly significant activity correlation,vith b enflumetol (P < 0.001) and to a similar degree,vith mefloquine (P < 0.001), reflecting a close relationship of DBB with the class II aryl amino alcoho l blood schizontocides. A less distinct association was also found with art emisinin, which was significant only at the EC50 level, and there was no co rrelation at all with chloroquine. DBB is a promising antimalarial compound that merits further investigation in order to define its practical therape utic potential.