Interaction of new dinuclear platinum complexes effective to cisplatin-resistant tumor cell lines with DNA.

点击翻译按钮获取中文摘要

Cisplatin is one of the most widely used anticancer agents. A current challenge in platinum bioinorganic chemistry is to design effective anticancer agents overcoming cisplatin resistance, based on the detailed knowledge of apoptosis attributable to DNA lesion by platinum binding. The purpose of this research project is to elucidate the differences of the interaction mode of some new dinuclear platinum complexes and that of cisplatin.The following results have been obtained.(1)New dinuclear platinum complexes with hydroxo-and pyrazolato-bridges were prepared and they induced apoptosis in the wild-type L 1210 and its cisplatin resistant cell lines.(2)Proton-assist square-planar platinum(II) substitution reaction in the dinuclear complexes was analyzed kinetically in the presence of sodium chloride.(3)Uptake of platinum atom by tumor cells was investigated by atomic absorption spectrometry, and intracellular platinum level was higher in the dinuclear complexes than in cisplatin.(4)Since the dinuclear complexes showed not only coordination binding with DNA but also non-covalent interactions, the DNA binding mode of dinuclear complexes is different from that of cisplatin. Effectiveness of the dinuclear complexes to the cisplatin resistant tumor cells seems to be attributed to this different binding mode with DNA.This research promises to lead to the development of new generation of anticancer agents overcoming cisplatin resistance.