Inhibition of lipoxygenase (LOX) and anticancer activity caused by gold(I) mixed ligands complexes of triphenylphosphine and thioamides

J Enzyme Inhib Med Chem. 2011 Aug;26(4):592-7. doi: 10.3109/14756366.2010.529807. Epub 2010 Nov 19.

Abstract

Four mixed ligand gold(I) complexes with the thioamides 2-mercapto-thiazolidine (mtzdH), 2-mercapto-benzothiazole (mbztH) and 5-chloro-2-mercapto-benzothiazole (ClmbztH) and triphenylphosphine (tpp) of formulae [Au(tpp)Cl] (1) [Au(tpp)(mtzd)] (2), [Au(tpp)(mbzt)] (3) and [Au(tpp)(Clmbzt)] (4), already known, were used to study their mechanism of inhibition activity towards the catalytic oxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX), kinetically and theoretically. The results are compared to those of cisplatin. In addition, the anticancer cell screening results against leimyosarcoma (LMS) cells have shown that 2-4 complexes were more active than cisplatin. The uptake of complexes in LMS cells were also studied with electrospray ionisation mass spectrometry spectroscopy.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Computational Biology
  • Drug Screening Assays, Antitumor
  • Gold / chemistry*
  • Leiomyosarcoma / drug therapy*
  • Leiomyosarcoma / enzymology
  • Leiomyosarcoma / pathology
  • Ligands
  • Lipoxygenase / metabolism*
  • Models, Molecular
  • Molecular Structure
  • Organogold Compounds / chemical synthesis
  • Organogold Compounds / chemistry
  • Organogold Compounds / pharmacology*
  • Organophosphorus Compounds / chemistry*
  • Rats
  • Rats, Wistar
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thioamides / chemistry*

Substances

  • Antineoplastic Agents
  • Ligands
  • Organogold Compounds
  • Organophosphorus Compounds
  • Thioamides
  • triphenylphosphine
  • Gold
  • Lipoxygenase