Platinum Metals Rev., 2002, 46, (4), 166
Platinum metals in Biological and Medicinal Chemistry
The Eighth International Conference on the Chemistry of the Platinum Group metals provided an ideal opportunity for researchers to report their latest results on research and development in the field of biological and medicinal chemistry with respect to the platinum metals. A number of exciting new directions have emerged in this field, and these are summarised below.
Professor J. K Barton (Caltech, U.S.A.) opened the proceedings, describing the elegant use of met-allointercalators to probe charge migration through DNA. DNA base mismatches and drug lesions (including those from cisplatin) on DNA can be characterised using this method. Her research group is currently embarking on exciting in vitro Cell studies using these novel probes.
The current status of several platinum drugs in clinical studies was reviewed by L. R. Kelland (St. George's Hospital Medical School, London, U.K.) who described the challenge of drug resistance that needs to be faced in future drug development. While cisplatin and oxaliplatin remain successful in the clinic, novel drugs such as JM216 and BBR3464 are currently under evaluation. Professor T. G. Appleton (University of Queensland, Australia) described the complex reactions with endogenous thiols that contribute to tumour resistance, and their examination using NMR techniques.
While Platinum drugs are the major research thrust of platinum metals in medicinal chemistry, the emergence of several promising ruthenium complexes with antimetastatic and antitumour activity was described by Professors G. Sava (University of Trieste, Italy) and P. J. Sadler (University of Edinburgh, U.K.), respectively. Complexes trialled by Sava have been shown to localise in the lung basement membranes, not in DNA like many Platinum drugs, thus preventing lung cancer metastasis. Sadler described the development of Ru(II) arene complexes with reduced toxicity, non-cross-resistance and a different spectrum of activity to Platinum compounds. Structure-activity relationships have been developed and highly selective DNA binding has been demonstrated. While it is clear that the development of further Platinum chemofherapeutics is an ongoing endeavour, the emergence of active ruthenium compounds with the potential to enter clinical trials demonstrates that the medicinal chemistry of the Platinum metals now has even wider potential.
Matt Hall is a Ph.D. student at the Centre for Heavy metals Research, University of Sydney, working on the biological fate of Pt(IV) antitumour complexes under the supervision of Professor Trevor W. Hambley. His interests are in bioinorganic chemistry, the biological fate of metals in medicine, and spectroscopy in Cellular and biological systems.
Matt Hall is the joint winner of the Platinum metals Review PGM8 conference student article competition.