ABSTRACT
Platinum and the platinum group metals (Ru, Os, Rh, Ir, and Pd) have a strong binding capacity for the electron donor groups in amino acids and have the ability to form chelates. This behavior determines their inactivating effect on enzymes and cell division and, in turn, makes them potential antibacterial and chemotherapeutic agents, as well as immunosuppressants (1-3). Platinum and its complexes stand out especially among platinum group metals for their activity in biological systems. From the perspective of occupational medicine, platinum salts represent a serious hazard, causing asthma, rhinitis, urticaria, and dermatitis. Platinum coordination complexes, a relatively new class of drugs with significant antitumor activity, appear to selectively interact with cellular DNA. Specifically, such activity is found in the neutral platinum complexes, and in the cis, e.g., cisplatin, or cis-Pt(NH3)2Cl2, rather than trans isomers. Cisplatin binds to DNA by forming intrastrand crosslinks in which the two chlorine atoms on cisplatin are replaced by nitrogen atoms of adjacent guanine residues on the same DNA strand. As are most other anticancer drugs, cisplatin has also shown to be mutagenic and moderately carcinogenic in animals (4). Also pronounced nephrotoxicity and neurotoxicity side effects in humans led to the development of second-generation drugs; when malonate derivatives (carboplatin) replaced the original chloride (cisplatin), toxic side effects were significantly reduced, while the antitumor activity was retained (5). A different spectrum of antitumor activity was recently observed with bis(platinum) complexes (homodinuclear Pt,Pt compounds), which proved effective in the treatment of cancer cells against which cisplatin is ineffective (6,7). This widening spectrum of antiproliferative effects has placed platinum compounds among the most active and widely used clinical agents for the treatment of advanced cancer.
