Activity of quinoline-containing antimalarials against chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro.
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-aminoquinolines, 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.
Geary
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TG
Department of Microbiology and Public Health, Michigan State University, East Lansing 48824-1101.
Divo
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AA
Jensen
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JB
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004351:Drug Resistance; D008826:Microbial Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011319:Primaquine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*
D000962:Antimalarials; D011804:Quinolines; D002738:Chloroquine; D011319:Primaquine; C007278:desethylchloroquine