A categorization of metal anticancer compounds based on their mode of action.

The development of new metal anticancer compounds is a challenge for inorganic chemists. We have to face the fact that four decades of research in this field have only produced a small number of clinically used compounds, most often developed through serendipity rather than through rational chemical design. Nevertheless, by virtue of the wealth of knowledge acquired in these years, medicinal inorganic chemistry is probably mature for making significant steps forward and there are great expectations for future developments. With the aim of contributing to the rationalization of this field, we suggest here a categorization of metal anticancer compounds into five classes based on their mode of action: (i) the metal has a functional role, i.e. it must bind to the biological target; (ii) the metal has a structural role, i.e. it is instrumental in determining the shape of the compound and binding to the biological target occurs through non-covalent interactions; (iii) the metal is a carrier for active ligands that are delivered in vivo; (iv) the metal compound is a catalyst; and (v) the metal compound is photoactive and behaves as a photo-sensitizer. Selected examples for each category are given. The few metal anticancer drugs that are in clinical use are all believed to be functional compounds. Our classification, that is clearly focused on the metal compound and is independent from the nature of its bio-target(s)-most often still unknown-has the purpose of providing an intellectual tool that might be helpful in the rational development of new drugs.