Novel Cis- and Trans-Configured Bis(oxime)platinum(II) Complexes: Synthesis, Characterization, and Cytotoxic Activity

Novel cis- and trans-configured bis(oxime)platinum(II) complexes
have been synthesized and characterized by elemental analyses, IR,
electrospray ionization mass spectrometry, multinuclear (1H, 13C, and 195Pt) NMR spectroscopy, and, in
five cases, by X-ray diffraction. Their cytotoxicity was studied in
the cisplatin-sensitive CH1 cell line as well as in inherently cisplatin-resistant
SW480 cancer cells. Remarkably, every single dihalidobis(oxime)platinum(II)
complex (with either a cis or trans configuration) shows a comparable
cytotoxic potency in both cell lines, indicating a capacity of overcoming
cisplatin resistance. Particularly strong cytotoxicities were observed
in the case of trans-[PtCl2(R2CNOH)2] (R = Me, n-Pr, i-Pr) with IC50 values in the high nanomolar
concentration range in both CH1 and SW480 cancer cells. These complexes
are as potent as cisplatin in CH1 cells and up to 20 times more potent
than cisplatin in SW480 cells. In comparison to transplatin, the novel
compounds are up to 90 (CH1) and 120 times (SW480) more cytotoxic.
The previously reported observation that the trans geometry yields
a more active complex in the case of [PtCl2(Me2CNOH)2] could be confirmed for at least two structural
analogues.