Generation of free radicals by simple prenylated hydroquinone derivatives, natural antitumor agents from the marine urochordate Aplidium californicum.

The redox properties of simple prenylated hydroquinone derivatives with cytotoxic properties have been studied by absorption and ESR spectroscopies. Both methods evidenced an autoxidation process in which the hydroquinones give rise to a semiquinone radical. Molecular oxygen is the electron acceptor, as demonstrated by spin trapping. No secondary radicals were found in the ESR spectra, either in the presence of hydroxyl anion (alkaline medium) or in the presence of glutathione. Nevertheless, a redox cycle can be initiated by glutathione, giving rise to substantial free-radical production. Thus, although not fully elucidated, the antitumor properties of the three hydroquinones described here can be correlated with their redox properties and their reactivity with thiol-containing peptides such as glutathione.