Activity of quinoline-containing antimalarials against chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro

Abstract

9 quinoline-containing antimalarials and the phenanthrene methanol halofantrine were tested in vitro against 6 strains of Plasmodium falciparum with known sensitivity to chloroquine. Sensitivity to chloroquine was not uniformly associated with sensitivity to mepacrine (quinacrine), halofantrine, SN-12108 or SN-6911 (3-methylchloroquine, sontochin). Amodiaquine was slightly less potent with chloroquine-resistant strains, whereas SN-12309 closely resembled chloroquine in the pattern of sensitivity. (Bis)desethylchloroquine was nearly as potent as chloroquine against chloroquine-sensitive strains but was about 10-fold less potent than the parent drug against chloroquine-resistant strains. 2 8-aminoquinplines, primaquine and pamaquine, were more potent against chloroquine-resistant than chloroquine-sensitive strains. The mutation(s) responsible for chloroquine resistance in P. falciparum greatly reduce(s) the sensitivity to a major metabolite of the drug but also generate(s) parasites which are more susceptible to a different class of drugs, the 8-aminoquinolines. © 1987.