MACROMOLECULAR METAL-COMPOUNDS IN CANCER-RESEARCH - CONCEPTS AND SYNTHETIC APPROACHES

The anticancer activity of metal compounds has been a topic of major i nterest in drug research for two decades- Platinum compounds, in parti cular, including cisplatin (cis-diamminedichloroplatinum(II)) and seco nd generation derivatives, have for many years been among the leading drugs administered in clinical cancer therapy, although excessive toxi city, induction of drug resistance, and other formidable, detrimental side effects continue to militate against efficacious utilization and achievement of satisfactory cure rates. Adding to the toxicity problem , most bioactive metal complexes dissolve poorly, if at all, in aqueou s media, possess low stability in solution, undergo rapid depletion fr om central circulation, and often times are prevented from smooth cell entry by molecular charge or polarity. The concept of polymer-drug co njugation, designed to overcome the pharmacokinetic barriers to satisf actory clinical chemotherapy with present-day anticancer drugs, is Fin ding increasing acceptance in biomedical research. The concept has bee n utilized in our laboratory for the purpose of enhancing the effectiv eness of metal-containing carcinostatic agents. In the present communi cation we demonstrate the practicability of synthesizing platinum-, ir on-, and tin-containing polymer conjugates that are biodegradable, dis solve completely in water, and are structurally designed so as to perm it release of the active metal compound in the biological environment. Following a brief review of initial results, we discuss selected synt hetic approaches and obtained conjugates, in which the metals are boun d to polymer attached ligands as dichloroplatinum(II), di-eta5-cyclope ntadienyliron, and diorganotin(IV) moieties.