Metal complexes as anticancer agents. An aspect of applied bioinorganic chemistry.

596

Abstracts

PO03 METAL COMPLEXES AS ANTICANCER AGENTS. AN ASPECT OF APPLIED BIOINORGANIC CHEMISTRY B.K. Keppler.

Anorganisch-Chemisches Institut der Universiti~tHeMelberg, lm Neuenheimer Feld 270, D-W-6900 Heidelberg, Germany. Cisplatin, cis-diamminedichloroplatinum(II), is among the first drugs from inorganic chemistry to have come under routine clinical use in medical oncology. It is active against testicular carcinomas, ovarian carcinomas, tumors of the head and neck, and bladder tumors. However, there is no or only insufficient antitumor activity in tumors which account for the major share of cancer mortali~ today, e.g. lung tumors and gastrointestinal tumors. Direct derivatives of cisplatin such as carboplatin have only led to reductions in drug toxici~. New metal complexes are now being developed to supplement the spectrum of indication of platinum complexes. Among non-platinum complexes, budotitane (INN), cis-diethoxybis(1-phenvlbutane-l,3-dionato)titanium(IV), Figure 1, is among the most advanced [1]. Budotitane is highly active in severn transplantable tumors and shows promising effects in an autochthonous colorectal tumor model, which is highly predictive for the clinical situation. Side-effects include mild hepatotoxicity and nephrotoxicity. These findings have been confirmed in clinical phase I studies. A phase II study is in preparation. Other promising metal complexes include ruthenium complexes, e.g. trans-imidazolium-bisimidazoletetrachlororathenate(III), HIm(RuIm 2C14), ICR, Figure 1, which also show good activib, in autochthonous col'orectal tumors of the rat [2]. •

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In what is known as drug targeting platinum complexes are linked with carrier systems to achieve an accumulation in particular organs and tissues. Important examples include platinum complexes with osteotropic properties, e.g. AMDP, cis-diammine[nitrilotris(methvlphosphonato)(2-)-O l,N ~]platinum(II), Figure 1, [31. " 1. B.K. Keppler and M.E. Heim, Drugs of the Future, 13, 5-6, 637-652 (1988). 2. B.K. Keppler, M. Henn, U.M. Juhl, M.R. Berger, R. Niebl, and F.E Wagner, Progress in Clinical Biochemistry and Medicine, 10, 41-69 (1989). 3. T. Klenner, F. Wingen, B.K. Keppler, B. Krcmpien, and D. SchmS.hl, J. Cancer Res. Clin. OncoL, 116, 341-350 (1990).