Multiple Recognition of DNA by dinuclear platinum complexes with effective cell growth inhibition in cisplatin resistant cell lines

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Both mechanisms of anti-tumor activity and cellular resistance to platinum complexes are believed to be related with coordination binding mode of platinum complexes with DNA. Polynuclear complexes are expected to interact variously with DNA and to have different mechanism of action from that of mononuclear complexes such as cisplatin, one of the most effective anti-tumor agents. In an attempt to search for more active platinum complexes and to overcome cisplatin resistance, we have developed a dinuclear platinum(II) cation complex, [{cis-Pt(NH_3)_2}_2(μ-pyrazolato) (μ-OH)](NO_3)_2 (AMPZ) and its derivatives using pyrazole analogues as bridging ligands. These platinum complexes were effective to cisplatin-resistant tumor cell lines. AMPZ was found to interact covalently and non-covalently with DNA. In this study we focused to non-covalent binding mode of AMPZ with DNA and investigated with various methods.The non-covalent binding mode of AMPZ with DNA has been found to an electrostatic interaction. It remains to be elucidated whether the anti-tumor activity of AMPZ is attributed to the non-covalent binding of AMPZ with DNA or not.