The Therapeutic Potential in Cancer of Terpyridine-Based Metal Complexes Featuring Group 11 Elements

ChemMedChem. 2024 May 17;19(10):e202300645. doi: 10.1002/cmdc.202300645. Epub 2024 Feb 28.

Abstract

Terpyridine-based complexes with group 11 metals emerge as potent metallodrugs in cancer therapy. This comprehensive review focuses on the current landscape of anticancer examples, particularly highlighting the mechanisms of action. While Cu(II) complexes, featuring diverse ancillary ligands, dominate the field, exploration of silver and gold species remains limited. These complexes exhibit significant cytotoxicity against various cancer cell lines with a commendable selectivity for non-tumorigenic cells. DNA interactions, employing intercalation and groove binding, are pivotal and finely tuned through terpyridine ligand functionalization. In addition, copper complexes showcase nuclease activity, triggering apoptosis through ROS generation. Despite silver's high affinity for nitrogen donor atoms, its exploration is relatively sparse, with indications of acting as intercalating agents causing DNA hydrolytic cleavage. Gold(III) compounds, overshadowing gold(I) due to stability concerns, not only intercalate but also induce apoptosis and disrupt the mitochondrial membrane. Further investigations are needed to fully understand the mechanism of action of these compounds, highlighting the necessity of exploring additional biological targets for these promising metallodrugs.

Keywords: Biological activity; Cancer; DNA-binding; Group 11; Terpyridine.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Copper / chemistry
  • Copper / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Neoplasms* / drug therapy
  • Neoplasms* / pathology
  • Pyridines* / chemical synthesis
  • Pyridines* / chemistry
  • Pyridines* / pharmacology
  • Structure-Activity Relationship