Photophysical, photochemical and photobiological studies of 4'-methylangelicins, potential agents for photochemotherapy.

Abstract

In order to study the relationship between certain photophysical and photochemical properties of furocoumarins and their photobiological activities, the quantum yields of the formation of excited triplet states, the capacity to generate singlet oxygen in vitro and the effect of oxygen on photoinduced cell killing and on the induction of cytoplasmic "petite" mutations in Saccharomyces cerevisiae were determined for a series of 4'-methylangelicins and 3-carbethoxypsoralen (3-CPs). The capacity to generate singlet oxygen, in good agreement with the photophysical data, correlates well with the oxygen effect observed on the lethality of Saccharomyces cerevisiae shown by the various compounds and followed the ranking order 3-CPs greater than 4',4-dimethylangelicin greater than 4'-methylangelicin greater than 4',5-dimethylangelicin. On the other hand the oxygen effect on the induction of cytoplasmic "petite" mutations on yeast appears much less pronounced than that shown on survival. Concerning other photobiological properties previously studied no correlation was observed between the capacity to generate singlet oxygen in vitro and the skin photosensitizing activity of the compounds. Moreover, the generation of singlet oxygen by furocoumarins does not appear as the main cause for the photoinduction of skin tumors in mice.