Analogues of N-benzyloxydihydrotriazines: in vitro antimalarial activity against Plasmodium falciparum.

The antimalarial activities of a series of chlorophenyloxyalkoxy and chlorophenalkoxy N-substituted diamino-dihydrotriazines were determined in vitro against three strains of Plasmodium falciparum (Malayan Camp, Vietnam Smith, FCB) with diverse levels of resistance to chloroquine, pyrimethamine, and cycloguanil. Parasite viability was assayed by the inhibition of the uptake of radiolabelled hypoxanthine. Most of the ID-50S of these compounds were less than 1.0 ng ml-1. Consistent differences in sensitivities to these compounds were observed and appeared to be strain related. The Malayan Camp was the most sensitive and Vietnam Smith was the least sensitive. These differences appeared to be related primarily to an inherent sensitivity of a particular strain to the series of analogues examined rather than to a pattern of cross-resistance to chloroquine, pyrimethamine, or cycloguanil.