Development and Current Status of Unconventional Platinum Anticancer Complexes

Abstract

Cisplatin is routinely employed for the treatment of testicular, ovarian cancer and head/neck tumors. Typical doses administrated to patients are 100 mg/day for up to five days. It is believed that the mechanism of action appears to be the binding of cis-Pt(NH3)(2) unit to DNA at two neighboring guanine bases. In the years following the introduction of cisplatin, the design of new platinum anticancer drugs concentrated mainly on direct cisplatin analogies, which stuck to the set of structure-activity relationships summarized by Clear and Hoeschele in 1973. Lately, some pioneering strategies towards the synthesis of novel platinum anticancer drugs based on the improved understanding of the mechanism of platinum resistance have emerged. Those are based on either changing the coordinated nitrogen ligand or altering the leaving groups. Other strategies have been shifted to discover "non classical" drugs that can act in a way different from cisplatin. Abnormal structures that violate the empirical structure-activity relationships of platinum compounds and multinuclear complexes are examples of these compounds. Several review articles appeared during recent years dealing with the synthesis, preclinical screening, and mechanism of action of platinum-based anticancer drugs. In this review, the progress in the field of anticancer chemistry based on unconventional platinum antitumor agents during the last 10 years will be highlighted. Most of the complexes that illustrate the recent and the previous prominent strategies will be presented.