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.

Special Issue "Cisplatin in Cancer Therapy: Molecular Mechanisms of Action 3.0".

The year 2023 marks the 45th year since FDA approval of cisplatin as an anticancer drug, and, at present, it is widely used against a spectrum of human tumors, including early-stage ovarian cancer, non-small cell lung cancer (typically developed by smokers), head and neck, and advanced bladder cancer [...

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.

Effect of chirality on the anticancer activity of Pt(II) and Pt(IV) complexes containing 1,2 and 1,2 enantiomers of the -1,2-diamino-4-cyclohexene ligand (DACHEX), an analogue of diaminocyclohexane used in oxaliplatin.

Six enantiomerically pure, oxaliplatin-like, platinum compounds (two platinum(II) and four platinum(IV)), all containing unsaturated cyclic diamine -1,2-diamino-4-cyclohexene (DACHEX) as a substitute for the -1,2-diaminocyclohexane used in oxaliplatin, were investigated. The complexes were characterized by elemental analyses, ESI-MS, and H-NMR spectroscopy. For the four Pt(IV) complexes the electrochemical redox behaviour, investigated by cyclic voltammetry, showed that all complexes possess reduction potentials suitable for activation .

A [Pt(cis-1,3-diaminocycloalkane)Cl] analog exhibits hallmarks typical of immunogenic cell death inducers in model cancer cells.

The platinum drugs belong to prevailing chemotherapeutics used in the treatment of cancer. At present, however, the search for new anticancer metal-based drugs that operate by the mechanisms distinct from those of the conventional chemotherapeutics is very active. Furthermore, it has been demonstrated that cytotoxic chemotherapy and immunotherapy may exert a highly synergistic anticancer activity.