Antimalarial activity of Mannich bases derived from 4-(7'-bromo-1',5'-naphthyridin-4'-ylamino)phenol and 4-(7'-trifluoromethylquinolin-4'-ylamino)phenol against Plasmodium falciparum in vitro.
Mono- and di-Mannich bases derived from 4-(7'-bromo-1',5'-naphthyridin-4'-ylamino)phenol and 4-(7'-trifluoromethylquinolin-4'-ylamino)phenol were assayed for antimalarial activity (using an in vitro radioisotopic technique) against two isolates of Plasmodium falciparum. Many from these two series of compounds had an IC50 value (concentration of compound causing 50% inhibition of 3H-hypoxanthine incorporation) comparable to or better than those of mefloquine and amodiaquine, for both a chloroquine-sensitive isolate (FCQ-27) and the chloroquine-resistant isolate (K1). At least one compound, 2,6-bis (piperidin-1''-ylmethyl)-4-(7'-trifluoromethylquinolin -4'-ylamino)phenol (TN112), showed significant superior activity to the three antimalarials chloroquine, mefloquine and amodiaquine against both isolates. (Statistically superior activity compared to these three antimalarials was found for TN112, except that against the K1 isolate its activity was just outside the range of significance relative to mefloquine.) Some of the 7-bromo-1,5-naphthyridine Mannich bases were appreciably less toxic in mice than amodiaquine.
Scott
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HV
Army Malaria Research Unit, Milpo, Ingleburn, New South Wales, Australia.
Tan
W L
WL
Barlin
G B
GB
D000588:Amines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D007928:Lethal Dose 50; D008352:Mannich Bases / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D009287:Naphthyridines / Q000378:metabolism; D010636:Phenols / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism
D000588:Amines; D000962:Antimalarials; D008352:Mannich Bases; D009287:Naphthyridines; D010636:Phenols