Interactions with DNA Models of the Oxaliplatin Analog (-1,3-DACH)PtCl.

It is generally accepted that adjacent guanine residues in DNA are the primary target for platinum antitumor drugs and that differences in the conformations of the Pt-DNA adducts can play a role in their antitumor activity. In this study, we investigated the effect of the carrier ligand -1,3-diaminocyclohexane (-1,3-DACH) upon formation, stability, and stereochemistry of the (-1,3-DACH)PtG and (-1,3-DACH)Pt(d(GpG)) adducts (G = 9-EthlyGuanine, guanosine, 5'- and 3'-guanosine monophosphate; d(GpG) = deoxyguanosil(3'-5')deoxyguanosine). A peculiar feature of the -1,3-DACH carrier ligand is the steric bulk of the diamine, which is asymmetric with respect to the Pt-coordination plane.

Cisplatin and zoledronic acid: two drugs combined in a Pt(II) complex with potential antitumor activity towards bone tumors and metastases.

Treatment of primary bone malignancies comprises surgery, radiotherapy, chemotherapy, and analgesics. Platinum-based chemotherapeutics, such as cisplatin, are commonly used for the treatment of bone cancer but, despite their success, outcomes are limited by toxicity and resistance. Recently, dinuclear Pt complexes with a bridging geminal bisphosphonate ligand proved to be endowed with selective accumulation in bone tumors or metastases leading to improved efficacy and reduced systemic toxicity.

Crystal Structure of the Human Copper Chaperone ATOX1 Bound to Zinc Ion.

The bioavailability of copper (Cu) in human cells may depend on a complex interplay with zinc (Zn) ions. We investigated the ability of the Zn ion to target the human Cu-chaperone Atox1, a small cytosolic protein capable of anchoring Cu(I), by a conserved surface-exposed Cys-X-X-Cys (CXXC) motif, and deliver it to Cu-transporting ATPases in the trans-Golgi network. The crystal structure of Atox1 loaded with Zn displays the metal ion bridging the CXXC motifs of two Atox1 molecules in a homodimer.

Improvement of Kiteplatin Efficacy by a Benzoato Pt(IV) Prodrug Suitable for Oral Administration.

Kiteplatin, [PtCl(-1,4-DACH)] (DACH = diaminocyclohexane), contains an isomeric form of the oxaliplatin diamine ligand -1,2-DACH and has been proposed as a valuable drug candidate against cisplatin- and oxaliplatin-resistant tumors, in particular, colorectal cancer. To further improve the activity of kiteplatin, it has been transformed into a Pt(IV) prodrug by the addition of two benzoato groups in the axial positions. The new compound, ,,-[PtCl(OBz)(-1,4-DACH)] (; OBz = benzoate), showed cytotoxic activity at nanomolar concentration against a wide panel of human cancer cell lines.