Resveratrol (trans-3,4′,5-trihydroxystilbene), a naturally occurring hydroxystilbene,
is considered an essential antioxidative constituent of red wine and many medicinal
plants. Moreover,
resveratrol, its metabolite piceatannol, and higher hydroxylated analogues were
reported to have cytotoxic activities. As a key factor for their activity, the hydroxyl
groups are considered
[1]. Therefore, one can wonder whether structures with more hydroxyl groups will have
a more potent antioxidant and cytotoxic effect. Moreover, is there a link
between antioxidant and cytotoxic activity? We have synthesized several other
polyhydroxylated resveratrol analogues and studied their pro-/antioxidant and cytotoxicity
properties to answer
this question. Our experiments suggested that not only the number of hydroxyl
groups and their disposition in aromatic rings play an important role. Our experiments
started from the
mitochondrial model and showed that oxidation of ortho-hydroxystilbenes (e.g.,
piceatannol) results in cytotoxic ortho-semiquinones production. Further investigations
revealed that these
intermediates undergo redox-cycling, consuming additional oxygen and forming cytotoxic
oxygen radicals. In contrast, compounds without such substitution patterns, (e.g.,
resveratrol) did not
show such activity [2]. Following this path, we have performed several in vitro studies employing different
cancer cell models showing different cytotoxic effects
exerted by resveratrol and analogues [3], [4]. In this talk, our results will be confronted with findings from other groups. The
results
of our investigation suggest that resveratrol has an optimal structure combining
antioxidant and cytostatic properties. A further increase in the number of hydroxyl
groups may result in
pro-oxidative activity that is harmful to cells.
