Synthesis and characterization of platinum(IV) anticancer drugs with functionalized aromatic carboxylate ligands: influence of the ligands on drug efficacies and uptake

J Med Chem. 2005 Dec 15;48(25):8060-9. doi: 10.1021/jm0506468.

Abstract

A series of trans-platinum(IV) complexes with functionalized aromatic carboxylate ligands, cis,cis,trans-Pt(NH3)2Cl2(CO2C6H4R)2 (R = H (3), p-vinyl (4), p-methoxy (5), p-iodo (6), p-cyano (7), or o-carboxyl (8)) was synthesized and characterized by spectroscopic methods. Crystal structures of 3, 4, 7, and 8 were obtained, which revealed that their structural conformations were influenced by intramolecular H-bonding interactions. The complexes were evaluated for cellular uptake and inhibition of cell proliferation against a panel of lung, colon, and breast carcinoma cell lines. The functionalization of the aromatic carboxylate ligand was found to have a profound influence on the uptake, and hence, efficacy, of this class of complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Benzoates / chemistry*
  • Cell Line, Tumor
  • Chelating Agents / chemical synthesis
  • Chelating Agents / pharmacology
  • Crystallography, X-Ray
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor
  • Humans
  • Hydrogen Bonding
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Molecular Structure
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / metabolism
  • Organoplatinum Compounds / pharmacology
  • Phthalic Acids / chemistry*
  • Structure-Activity Relationship

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Benzoates
  • Chelating Agents
  • Ligands
  • Organoplatinum Compounds
  • Phthalic Acids