title: Activities of various 4-aminoquinolines against infections with chloroquine-resistant strains of Plasmodium falciparum.
abstract: The studies reported here stemmed from a personal report by Geiman on the capacity of the 4-aminoquinoline amodiaquin to inhibit in vitro maturation of ring stages of the chloroquine-resistant Monterey strain of Plasmodium falciparum. This observation, confirmed in owl monkeys infected with this strain, led to a comparison of the activities of chloroquine, amodiaquin, amopyroquin, and dichlorquinazine (12,278 RP) against infections with various chloroquine-susceptible and chloroquine-resistant strains. The results showed that: (i) these 4-aminoquinolines were essentially equally active against infections with chloroquine-susceptible strains and (ii) the activities of amodiaquin, amopyroquin, and dichlorquinazine were reduced significantly in the face of chloroquine resistance, but (iii) well-tolerated doses of these compounds would cure infections with strains that fully resisted treatment with maximally tolerated doses of chloroquine. Two other 4-aminoquinolines, SN-8137 and SN-9584, which also exhibited activity against chloroquine-resistant parasites in vitro, displayed curative activity in monkeys infected with a chloroquine-resistant strain. These observations show that there is cross-resistance among the 4-aminoquinolines, confirming earlier findings, but indicate that the dimensions of this phenomenon are sufficiently limited so that some derivatives are therapeutically effective against infections refractory to maximally tolerated doses of chloroquine.
mesh_terms: D000634:Aminoquinolines / Q000627:therapeutic use*; D000655:Amodiaquine / Q000627:therapeutic use; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D005260:Female; D000882:Haplorhini; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000634:Aminoquinolines; D000655:Amodiaquine; D002738:Chloroquine