Synthesis, characterization, and cytotoxicity of trifunctional dinuclear platinum complexes: Comparison of effects of geometry and polyfunctionality on biological activity

The synthesis of two new isomeric trifunctional dinuclear platinum complexe s of formula [{PtCl(NH3)(2)}mu-NH2(CH2)(6)NH2-{PtCl2(NH3)}](+) (1,2/c,c and 1,2/t,c) is reported. Their biological activity in selected human tumor ce ll lines sensitive and resistant to CDDP (cisplatin, cis-[Pt(NH3)(2)Cl-2]) is described and compared with the profile for their bifunctional analogues , [{cis/trans-PtCl(NH3)(2)}(2)mu-NH2(CH2)(6)NH2](2+). The trifunctional din uclear platinum complexes showed a unique profile of cytotoxicity against h uman cancer cell lines, with low resistance factors in A2780, CH1, and 41M cell. lines. The resistance factor is dependent on the geometry of the Pt c oordination spheres - suggesting that these may be associated with DNA-bind ing modes. Retention of activity against CDDP-resistant cell lines and a di fferent spectrum of activity compared to CDDP and also within different cla sses of polynuclear platinum complexes suggest that not only are they mecha nistically different from mononuclear platinum complexes but also each indi vidual class of polynuclear platinum structure may have its own unique char acter.