chapter  4
49 Pages

Chemical Mechanisms of the Bioeffects of Furocoumarins: The Role of Reactions with Proteins, Lipids, and Other Cellular Constituents

WithW. Robert Midden

This chapter examines the chemical reactions of furocoumarins that could be responsible for their biological effects. Since these oxidants can be produced in varying amounts by furocoumarins illuminated with UVA, it is reasonable to suspect that psoralen-induced lipid oxidation could be responsible for the cytotoxicity and perhaps other bioeffects of furocoumarins. Furocoumarins which have the fusion at 2,3 bond of the furan and the 6,7 bond of the coumarin are considered linear furocoumarins and are commonly called psoralens. Whether reactions with proteins, lipids, or some other molecular target are responsible for this lysis is unknown, but it is reasonably certain that it was not due to reactions with nucleic acids. A number of observations strongly support the hypothesis that modification of DNA is responsible for the lethal effect of furocoumarins in microorganisms as well as virus and sperm. Besides covalent binding to unsaturated fatty acids, oxidation of fatty acids may also occur in some cases, perhaps depending on the conditions.