A Multitarget Gold(I) Complex Induces Cytotoxicity Related to Aneuploidy in HCT-116 Colorectal Carcinoma Cells

Angew Chem Int Ed Engl. 2020 Sep 14;59(38):16795-16800. doi: 10.1002/anie.202006212. Epub 2020 Jul 30.

Abstract

A novel alkynyl phosphane gold(I) complex (trimethylphosphane)(3-(1,3-dimethylxanthine-7-yl)prop-1-yn-1-yl)gold(I) 1 displayed mutiple biological activites including selective proliferation inhibitory, anti-metastatic, and anti-angiogenic effects. The complex also induced effects related to aneuploidy in HCT-116 colon carcinoma cells, which might be mainly ascribed to the dysfunction of mitochondrial bioenergetics and downregulation of glycolysis. Induction of aneuploidy beyond a critical level can provide an effective strategy to target cancer, in particular colorectal tumours with a low tolerance of aneuploidy, and could be of relevance for 1 and other metallodrugs.

Keywords: aneuploidy; antitumor agents; gold complexes; inorganic medicinal chemistry; metallodrugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chickens
  • Chorioallantoic Membrane / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HCT116 Cells
  • Humans
  • Molecular Structure
  • Organogold Compounds / chemical synthesis
  • Organogold Compounds / chemistry
  • Organogold Compounds / pharmacology*
  • Ovum / drug effects
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Organogold Compounds
  • Reactive Oxygen Species