A focus on the biological targets for coinage metal-NHCs as potential anticancer complexes

J Inorg Biochem. 2021 Apr:217:111355. doi: 10.1016/j.jinorgbio.2021.111355. Epub 2021 Jan 20.

Abstract

Metal complexes of N-heterocyclic carbene (NHC) ligands are the object of increasing attention for therapeutic purposes. Among the different metal centres, interest on Au-based compounds started with the application as anti-arthritis drugs. On the other hand, Ag(I) antimicrobial properties have been known for a long time. For Au(I)/Au(III)-NHC and Ag(I)-NHC anti-tumour and anti-proliferative properties have been quite recently demonstrated. In addition to these and as for Group 11, copper is a much less investigated metal centre, but a few papers underline its pharmacological potential. This review wants to focus on the different biological targets for these metal-based compounds. It is divided into chapters which are respectively devoted on: i) mitochondria and thiol oxidoreductase systems; ii) other relevant enzymes; iii) nucleic acids. Examples of representative coinage NHCs for each of the targets are provided together with significant references on recent advances on the topic. Moreover, a final comment summarises the aspects enlightened by each chapter and provides some hints to better understand the metal-NHCs mechanistic behaviour based on structure-activity relationships.

Keywords: Gold; Metal-based complexes; Mode-of-action; N-heterocyclic carbene; Silver; Thioredoxin reductase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Coordination Complexes / therapeutic use*
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Metals, Heavy / chemistry
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology
  • Trypanocidal Agents / therapeutic use

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Enzyme Inhibitors
  • Metals, Heavy
  • Trypanocidal Agents