Novel platinum(II) derivatives of analogues of netropsin and distamycin: Synthesis, DNA binding and cytotoxic properties
Lee, M.; Simpson, J. E.; Burns, A. J.; Kupchinsky, S.; Brooks, N.; Hartley, J. A.; Kelland, L. R. Novel platinum(II) derivatives of analogues of netropsin and distamycin: Synthesis, DNA binding and cytotoxic properties. Med. Chem. Res. 1996, 6, 365-371.
A number of platinum(II) derivatives of analogues of the minor groove binding agents netropsin and distamycin have been synthesized. The platinum (II) atom is conjugated to either the Nor the C-terminus of the minor groove binder. These compounds were found to bind strongly and irreversibly to the minor groove of DNA, and they showed a preference for poly(dA-dT) over poly(dG-dC). Cytotoxicity studies performed against the growth of chronic human myeloid leukemia K562, human ovarian carcinoma A2780 and A2780cisR (cisplatin resistant) cells in culture showed these derivatives to have IC50 values that are generally higher than that for cisplatin itself.
Medicinal Chemistry Research