THE INVITRO AND INVIVO 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.