The Role of Platinum-DNA Lesions in the Inhibition of DNA Replication
Cytotoxicity and antitumor activity of platinum complexes are often sensitive to structural features of the platinum compound such as its isomerism, the number of leaving groups, and the nature of the stable ligand. Whereas cis-[Ptcl2(NH3)2] (cis-DDP) is an antitumor drug which is active against human and murine cancers, monofunctional compounds such as [PtCl(dien)]Cl and the trans isomer, trans-DDP, have no antitumor activity (Braddock et al., 1975; Macquet and Butour, 1983). During the reaction with DNA, the N(7) atoms of purine bases substitute the labile Cl ligands while the non-leaving group, NH3, remains bound to the metal. Non-leaving groups play an important role in modulating the antitumor activity of platinum compounds. For example, cell lines resistant to cis-DDP are not cross-resistant to platinum complexes with 1,2-diaminocyclohexane (DACH) (Burchenal et al., 1979). Platinum complexes with alkylamine and pyridine ligands are less antitumor than cis-DDP or inactive (Braddock et al., 1975; Meischen et al., 1976; Farrell et al., 1989).
KeywordsL1210 Cell Platinum Complex Platinum Compound Wild Type Bacterium Pyridine Ligand
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