Charge transfer and oxy radicals in antimalarial action. Quinones, dapsone metabolites, metal complexes, imunium ions, and peroxides

Abstract

A mechanism of action is proposed that encompasses almost all of the main categories of antimalarial agents: quinones and precursors, dapsone metabolites, metal complexes of thisemicarbazones and biguanides, imunium-type ions from acridines and quinolines, and peroxides. The toxic effect of the drugs is believed to result from the generation of reactive oxygen oxygen radicals that usually arise via charge transfer. Electrochemical studies (reduction potential and reversibility) were performed on a number of these agents. Reduction potentials range from −0.23 to −1.52 V. It is likely that the in vivo values are aprreciably more positive in certain cases.