4Z41: X-ray Structure Of The Adduct Formed In The Reaction Between Lysozyme And A Platinum(ii) Compound With A S,o Bidentate Ligand (9a=chloro- (1-(3'-hydroxy)-3-(methylthio)-3-thioxo-prop-1-en-1-olate-o,s)- (dimethylsulfoxide-s)-platinum(ii))

We recently characterized a series of novel platinum(II) compounds bearing a conserved O,S binding moiety as a bifunctional ligand and evaluated their solution behavior and antiproliferative properties in vitro against a representative cancer cell line. On the whole, those platinum compounds showed an appreciable stability in mixed dimethyl sulfoxide-aqueous buffers and promising in vitro cytotoxic effects; yet they manifested a rather limited solubility in aqueous media making them poorly suitable for further pharmaceutical development. To overcome this drawback, four new derivatives of this series were prepared and characterized based on a careful choice of substituents on the O,S bidentate ligand. The solubility and stability profile of these novel compounds in a reference buffer was determined, as well as the ligands' log Po/w value (Po/w = n-octanol-water partition coefficient) as an indirect measure for the complexes' lipophilicity. The antiproliferative properties were comparatively evaluated in a panel of three cancer cell lines. The protein binding properties of the four platinum compounds were assessed using the model protein hen egg white lysozyme (HEWL), and the molecular structures of two relevant HEWL-metallodrug adducts were solved. Overall, it is shown that a proper choice of the substituents leads to a higher solubility and enables a selective fine-tuning of the antiproliferative properties. The implications of these results are thoroughly discussed.
PDB ID: 4Z41Download
MMDB ID: 132225
PDB Deposition Date: 2015/4/1
Updated in MMDB: 2015/09
Experimental Method:
x-ray diffraction
Resolution: 1.89  Å
Source Organism:
Similar Structures:
Biological Unit for 4Z41: monomeric; determined by author and by software (PISA)
Molecular Components in 4Z41
Label Count Molecule
Protein (1 molecule)
Lysozyme C(Gene symbol: LYZ)
Molecule annotation
Chemicals (13 molecules)
* Click molecule labels to explore molecular sequence information.

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