New gold carbene complexes as candidate anticancer agents

Biometals. 2016 Oct;29(5):905-11. doi: 10.1007/s10534-016-9962-0. Epub 2016 Aug 6.

Abstract

Three structurally related gold(I) carbene complexes with bulky hydrophobic ligands i.e. 1-3 were investigated in solution for further consideration as candidate anticancer agents. Cytotoxic assays were subsequently conducted on bone marrow-derived preosteoclast cell line of human origin (FLG 29.1) and human colon cancer cells (HCT-116). A far greater cytotoxic activity was measured for compound 1 against HCT-116 cells compared to 2 and 3; conversely, all compounds were highly and similarly active against FLG 29.1 cells. Results obtained for the reaction of complexes 1 and 2 with RNase A documented the occurrence of a weak interaction with this model protein and the formation of a tiny amount of the corresponding adduct. Moreover, a certain reactivity of the complex 2 was also detected toward GSH. The general implications of the obtained results are discussed.

Keywords: Anticancer drugs; ESI–MS; Gold carbene; Protein interaction.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Filaggrin Proteins
  • Gold / chemistry*
  • Gold / pharmacology*
  • HCT116 Cells
  • Humans
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Methane / pharmacology
  • Mice
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • FLG protein, human
  • Filaggrin Proteins
  • carbene
  • Gold
  • Methane