The causal prophylactic activity of the novel hydroxynaphthoquinone 566C80 against Plasmodium berghei infections in rats.

Abstract

The influence of the novel hydroxynaphthoquinone 566C80 on exoerythrocytic development of Plasmodium berghei was examined in Brown Norway rats. The procedure employed was designed to identify residual activity of the drug against tissue merozoites emerging into the bloodstream and to distinguish this from any observed causal prophylactic activity against the liver stages. Single oral doses of 10 and 1 mg/kg of 566C80 administered 3 hours after sporozoite-inoculation were effective in preventing the appearance of a patent parasitaemia, while a dose of 0.1 mg/kg significantly reduced the severity of the ensuing blood infection. There was a pronounced residual effect of 566C80 against the blood forms at a dose of 10 mg/kg, a slight residual effect at a dose of 1 mg/kg, but no apparent residual effect at 0.1 mg/kg. At the time when EE merozoites would normally emerge into the bloodstream, an aliquot of blood was sub-inoculated into mice from sporozoite-infected, 566C80-treated rats. This procedure confirmed that 566C80 is active against the exoerythrocytic stages of Plasmodium berghei.