Monofunctional and Higher-Valent Platinum Anticancer Agents

Platinum compounds represent one
of the great success stories of
metals in medicine. Following the serendipitous discovery of the anticancer
activity of cisplatin by Rosenberg, a large number of cisplatin variants
have been prepared and tested for their ability to kill cancer cells
and inhibit tumor growth. These efforts continue today with increased
realization that new strategies are needed to overcome issues of toxicity
and resistance inherent to treatment by the approved platinum anticancer
agents. One approach has been the use of so-called “non-traditional”
platinum­(II) and platinum­(IV) compounds that violate the structure–activity
relationships that governed platinum drug-development research for
many years. Another is the use of specialized drug-delivery strategies.
Here we describe recent developments from our laboratory involving
monofunctional platinum­(II) complexes together with a historical account
of the manner by which we came to investigate these compounds and
their relationship to previously studied molecules. We also discuss
work carried out using platinum­(IV) prodrugs and the development of
nanoconstructs designed to deliver them in vivo.