French scientists are unravelling the anticancer secrets of ferrocenyl phenols.

Some breast cancer cells have oestrogen receptors and so natural oestrogen can stimulate their growth. A number of effective treatments are available for these hormone-receptor-positive breast cancers; one example being selective oestrogen receptor modulators such as tamoxifen, which can be used to occupy the hormone receptors, thus blocking oestrogen from them. But few effective therapies exist for hormone-independent breast cancers.

Recently, Gerard Jaouen and co-workers, from the Ecole Nationale Superieure de Chimie de Paris, found that ferrocenyl phenols can act against not only hormone-dependent but also hormone-independent breast cancer cells. Now they are discovering how these cytotoxic compounds work.

The key to this mystery seems to be the position of the hydroxyl group on the phenol ring. The most cytotoxic of the ferrocenyl phenols are those with the hydroxyl group at the para position. Jaouen's team found that meta-OH substitution not only dramatically reduced a phenol's binding affinity for one form of the oestrogen receptor, but also lowered its cytotoxicity in hormone-independent breast cancer cells.

Further experiments showed that para-substitution also had an effect on the phenols' electrochemical properties, and suggested that the para-OH substituted phenols oxidise to form quinone methide-type structures. A para-OH would allow greater resonance stabilisation of the radical intermediate on the way to these structures. The researchers propose that oxidative activation to quinone methide species could be 'a key' to the phenols' biological activity.

Freya Mearns