Photosensitizing properties of quinine and synthetic antimalarials

Quinine, an alkaloid that occurs in the bark of trees of the genus Cinchona, has been used for the treatment of malaria in humans for over 150 years. In 1888 it was reported that quinine was more toxic to plant tissues and frog eggs in the light than in the dark; thus it is probably one of the first pure compounds shown to be a photosensitizer for biological systems. During this century, because of the toxic side effects of quinine and the appearance of quinine-resistant malarial strains, a search was begun to identify synthetic antimalarial compounds with improved properties. A number have been identified and are now in widespread use; but like quinine, most of these are also photosensitizers. Because of the very large numbers of patients receiving antimalarials, many studies have been made of the photophysical, photochemical and photosensitizing properties of quinine and several of the most commonly used synthetic antimalarials (chloroquine, primaquine, quinacrine and mefloquine). The results of these studies are summarized in this review. Most antimalarials photosensitize in part by the generation of singlet oxygen, although free radical pathways may also be involved. The carcinogenic and photocarcinogenic properties of antimalarials and related compounds are briefly surveyed.