The in vitro and in vivo antimalarial activity of some Mannich bases derived from 4-(7'-trifluoromethyl-1',5'-naphthyridin-4'-ylamino)phenol, 2-(7'-trifluoromethyl-quinolin-4'-ylamino)phenol, and 4'-chloro-5-(7''-trifluoromethylquinolin-4''-ylamino)biphenyl -2-ols.
A series of di-Mannich base derivatives (4 and 5) from 4-(7'-trifluoromethyl-1',5'-naphthyridin-4'-ylamino)phenol and 2-(7'-trifluoromethylquinolin-4'-ylamino)phenol, respectively, and mono-Mannich base derivatives (6) from 4'-chloro-5-(7''-trifluoromethylquinolin-4''- ylamino)biphenyl-2-ol were assayed for activity against the chloroquine-sensitive (FCQ-27) isolate of cultured Plasmodium falciparum using the inhibition of uptake of radiolabelled hypoxanthine. All seven di-Mannich base derivatives (5) revealed a higher activity than chloroquine, whereas the di-Mannich base derivatives (4) were slightly less active (with some derivatives more active and some less active than chloroquine). The mono-Mannich base derivatives (6) were less active than chloroquine. Comparative tests of selected compounds of (4 and 5) using a morphological assay revealed no significant differences in activity between the chloroquine-sensitive (FCQ-27) and chloroquine-resistant (K-1) isolates. Selected di-Mannich bases (4 and 5) and the mono-Mannich bases 5-7''-bromo (and 7-trifluoromethyl)-1'',5''-naphthyridin-4''-ylamino)-3-(t- butylaminomethyl)-4'-chlorobiphenyl-2-ols (7, X = Br, CF3) markedly suppressed parasitaemia in Plasmodium vinckei vinckei infected mice when administered (i.p.) in a single dose of 200 mg kg-1.
Barlin
G B
GB
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT.
Jiravinyu
C
C
Butcher
G A
GA
Kotecka
B
B
Rieckmann
K
K
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D007042:Hypoxanthines / Q000378:metabolism; D016778:Malaria, Falciparum / Q000188:drug therapy; D008297:Male; D008352:Mannich Bases / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism
D000962:Antimalarials; D007042:Hypoxanthines; D008352:Mannich Bases; D002738:Chloroquine