Abstract

The human malaria parasite, Plasmodium falciparum, has been shown in vitro to be sensitive to lipophilic chelators with high metal-binding constants. Growth inhibition of the parasite correlates directly with the ability of the compound to chelate, and favorable activity has been demonstrated among the alkyl thiocarbamates, pyridine-N-oxides and quinolines. The 5-substituted 8-hydroxyquinolines and 2-mercaptoquinoline-N-oxide, which have had some use in medicine and cosmetics, possess these characteristics. They also exhibit active antimalarial effects in vitro at concentrations as low as 5 x 10^-8 M, making them more potent than quinine sulfate in the same system. Antimalarial effects are not antagonized by cobalt or potentiated by iron, but toxicity of the 5-substituted oxines to the parasite is increased by increasing oxygen levels in vitro.