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

Abstract

A series of di-Mannich base derivatives (4 and 5) from 4-(7′-trifluoromethyI-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.