NOVEL PLATINUM(II) DERIVATIVES OF ANALOGS OF NETROPSIN AND DISTAMYCIN- SYNTHESIS, DNA-BINDING AND CYTOTOXIC PROPERTIES

A number of platinum(II) derivatives of analogues of the minor groove binding agents netropsin and distamycin have been synthesized. The pla tinum (II) atom is conjugated to either the Nor the C-terminus of the minor groove binder. These compounds were found to bind strongly and i rreversibly to the minor groove of DNA, and they showed a preference f or poly(dA-dT) over poly(dG-dC). Cytotoxicity studies performed agains t the growth of chronic human myeloid leukemia K562, human ovarian car cinoma A2780 and A2780cisR (cisplatin resistant) cells in culture show ed these derivatives to have IC50 values that are generally higher tha n that for cisplatin itself.