Recent Developments in the Field of Tumor-Inhibiting Metal Complexes
25 years after the first approval of cisplatin in the clinic against a number of cancer diseases, cisplatin and related compounds continue to be among the most efficient anticancer drugs used so far. Efforts are focused to develop novel platinum- and non-platinum-based antitumor drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. In the field of non-platinum compounds exhibiting anticancer properties, ruthenium complexes are very promising, showing activity on tumors which developed resistance to cisplatin or in which cisplatin is inactive. Furthermore, general toxicity was found to be very low. The first ruthenium compound NAMI-A entered phase I clinical trials in 1999 as an antimetastatic drug, whereas the ruthenium complex KP1019 will enter phase I clinical trials in 2003 as an anticancer drug which is among others very active against colon carcinomas and their metastases. Remarkable progress is also seen in developing tumor inhibiting gallium compounds. One of them, KP46, will also enter phase I clinical trials in 2003. This article reviews briefly the achievements in the field of anticancer metal complexes focusing the discussion onto the impact of the group of Bioinorganic Chemistry at the Department of Inorganic Chemistry at the University of Vienna. The development of pH sensitive platinum prodrugs, platinum-based drug targeting strategies with low-molecular-weight carriers, kinetically inert platinum(IV) complexes, as well as tumor inhibiting non-platinum anticancer drugs based on ruthenium and gallium is covered in the following sections.
Galanski
M S
MS
Department of Inorganic Chemistry, University of Vienna, Vienna, Austria.
Arion
V B
VB
Department of Inorganic Chemistry, University of Vienna, Vienna, Austria.
Jakupec
M A
MA
Department of Inorganic Chemistry, University of Vienna, Vienna, Austria.
Keppler
B K
BK
Department of Inorganic Chemistry, University of Vienna, Vienna, Austria.
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000639:trends*; D015195:Drug Design; D006801:Humans; D008024:Ligands; D019216:Metals, Heavy / Q000737:chemistry* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D008024:Ligands; D019216:Metals, Heavy