Bis(dimethylsulfoxide)carbonateplatinum(ii), a new synthon for a low-impact, versatile synthetic route to anticancer Pt carboxylates

Dalton Trans. 2016 Jun 28;45(26):10752-60. doi: 10.1039/c6dt01689h.

Abstract

The work describes a new low-impact synthetic route to Pt(ii)-carboxylate complexes, a class of compounds provided with established anticancer activity. The process is based on the ligand substitution on [PtCO3(Me2SO-S)2] (), a new synthon that can be easily prepared in water with high yield, is stable as a solid, and is reactive in solution where all its ligands can be easily replaced. It reacts with acidic O-donors releasing CO2 as the only side-product, whose development also supplies a driving force toward the products. The substitution of carbonate led to new Pt-DMSO carboxylate complexes , while the total substitution of the ligands of complex gave new Pt-phosphino carboxylates in high yields. The X-ray crystal structures of complexes [Pt(d(-)-quinate-O,O')(Me2SO-S)2] (), [Pt(salicylate)(Me2SO-S)2] () and [Pt(salicylate)(PPh3)2] () were determined. The tests of the antiproliferative activity of complexes on two human tumoral cell lines, A2780 (cisplatin-sensitive) and SKOV-3 (cisplatin-resistant), showed that the PTA (PTA = 1,3,5-triaza-7-phosphaadamantane) complexes were the most active on both cell lines.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Carbonates / chemical synthesis
  • Carbonates / chemistry*
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic
  • Crystallography, X-Ray
  • Dimethyl Sulfoxide / chemical synthesis
  • Dimethyl Sulfoxide / chemistry*
  • Humans
  • Models, Molecular
  • Neoplasms / drug therapy
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology

Substances

  • Antineoplastic Agents
  • Carbonates
  • Carboxylic Acids
  • Organoplatinum Compounds
  • Dimethyl Sulfoxide