Novel platinum pyridinehydroxamic acid complexes: Synthesis, characterisation, X-ray crystallographic study and nitric oxide related properties

Herein, we describe the synthesis and characterisation of a novel class of PtII and PtIV pyridinehydroxamic acid (pyhaH) complexes of general formula cis-[PtIICl2(x-pyhaH)2] and cis-[PtIVCl4(x-pyhaH)2], respectively (where x = 3 or 4) in which the pyridinehydroxamic acid is coordinated to the platinum ion via the pyridine nitrogen only leaving the hydroxamic acid free to potentially release cytotoxic nitric oxide (NO). The crystal structure of the PtIV derivative, cis-[PtCl4(4-pyhaH)2] · 2CH3OH is reported. To establish the biological effect of the uncoordinated hydroxamic acid moiety in the PtII compounds synthesised, the corresponding pyridinecarboxylic acid (pycaH) complexes of general formula cis-[PtIICl2(x-pycaH)2] (where x = 3 or 4) and the PtII pyridine (py) complex, cis-[PtIICl2(py)2] were synthesised and served as reference standards. The NO-releasing properties of each of the PtII compounds, the pyhaH and the pycaH ligands were studied. The PtII pyridinehydroxamic acid derivatives were found to induce potent in vitro effects attributable to either NO-release from the hydroxamic acid moiety and/or stimulation of inducible nitric oxide synthase of endothelial cells.

On the premise that there is little or no evidence in the literature of nitric oxide (NO)-releasing platinum-based compounds, the NO-releasing ability of a novel series of platinum pyridinehydroxamic acid complexes are described with a view to advancing a new class of bifunctional metallodrug with dual DNA-binding and NO-releasing properties.Figure optionsDownload as PowerPoint slide