• cytotoxicity
• monohaloacetate
• oxaliplatin
• platinum(IV)
• prodrugs
• synthesis

Pt(IV) complexes are considered valuable prodrugs for their kinetic inertness, their ability to be reduced in cancer cells and the possibility of modulating axial ligands. Upon reaching tumour cells, they are activated by reduction, releasing axial ligands and the corresponding Pt(II) active species. Six oxaliplatin-based Pt(IV) complexes with monohaloacetate (MAA) ligands in axial position were synthesised. Monofluoroacetate (MFA), monochloroacetate (MCA), and monobromoacetate (MBA) were selected as bioactive molecules, allowing Pt(IV) complexes to show a dual action. MFA and MCA affect the Krebs cycle by inhibiting aconitase, while MBA causes oxidative damage to DNA. All the complexes were characterised through 1H-NMR, 13C-NMR and elemental analysis (CHN). Solubility in water was measured through 1H-NMR using dimethyl sulfone (DMSO2) as an internal standard. The logPo/w value was determined by ICP-OES and the stability of MAA complexes was studied in PBS and DMSO at 37°C through UV-vis spectroscopy. Reduction kinetics were measured with the same technique, using dithiothreitol (DTT) as a reducing agent. Finally, the biological activity of the compounds was evaluated in the A2780 cancer cell line under normoxic and hypoxic conditions. Despite cytotoxicity comparable to that of cisplatin has been evidenced in all cases, in hypoxic environment the most active is the MCA-monofunctionalised complex, while the less active one is the MFA-difunctionalised.