Photoreactivity of Phototoxic Antimalarial Compounds

Abstract

The photochemical reactivity of six phototoxic 2-arylquinolinemethanol antimalarials was examined to understand the chemical mechanism of reaction that causes the in vivo phototoxicity. All of these compounds were found to be photochemically reactive, giving products of photochemical fragmentation involving cleavage of the side chain. The products which are formed, the variation in product distribution with change of solvent and presence of thiols, and photolyses in deuterium-labeled solvents indicate that free radicals are involved in the photofragmentation. There is a good correlation between the quantum efficiency of the photofragmentation reaction and the phototoxicity of the compounds; the more phototoxic compounds react most efficiently, while the less phototoxic compounds react less efficiently. It appears that in vivo free radical reactions caused by the photofragmentation of these compounds are the source of their phototoxicity.