N-Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin

ChemMedChem. 2022 Sep 16;17(18):e202200345. doi: 10.1002/cmdc.202200345. Epub 2022 Aug 17.

Abstract

In recent years, the number of people suffering from cancer has risen rapidly and the World Health Organization and U.S. and European governments have identified this pathology as a priority issue. It is known that most bioactive anticancer molecules do not target a single protein but exert pleiotropic effects, simultaneously affecting multiple pathways. In our study, we designed and synthesized a new series of silver N-heterocyclic carbene (NHC) complexes [(NHC)2 Ag]+ [AgX2 ]- (X=iodide or acetate). The new complexes were active against two human breast cancer cell lines, MCF-7 and MDA-MB-231. These compounds showed multiple target actions as anticancer, by inhibiting in vitro the activity of the human topoisomerases I and II and interfering with the cytoskeleton dynamic, as also confirmed by in silico studies. Moreover, the antimicrobial activity of these silver complexes was studied against Gram-positive/negative bacteria. These dual properties provide a two-tiered approach, making these compounds of interest to be further deepened for the development of new chemotherapeutic agents.

Keywords: actin; breast cancer; docking studies; human topoisomerases; silver N-heterocyclic carbine complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates
  • Actins
  • Anti-Infective Agents* / pharmacology
  • Antineoplastic Agents* / pharmacology
  • Coordination Complexes*
  • Gram-Negative Bacteria
  • Gram-Positive Bacteria
  • Heterocyclic Compounds* / pharmacology
  • Humans
  • Iodides
  • Methane / analogs & derivatives
  • Methane / pharmacology
  • Silver / pharmacology

Substances

  • Acetates
  • Actins
  • Anti-Infective Agents
  • Antineoplastic Agents
  • Coordination Complexes
  • Heterocyclic Compounds
  • Iodides
  • carbene
  • Silver
  • Methane