Novel Anticancer NHC*-Gold(I) Complexes Inspired by Lepidiline A

Molecules. 2020 Jul 30;25(15):3474. doi: 10.3390/molecules25153474.

Abstract

N-Heterocyclic carbene gold(I) complexes derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*) represent a promising class of anticancer drugs. Complexes of the type NHC*-Au-L (L = Br-, I-, C≡C-R) and [NHC*-Au-L]+ (L = NHC*, PPh3) have been synthesised. The X-ray crystal structures of all gold(I) complexes are presented; aurophilic interactions were observed in five of the complexes. The anticancer activity was assessed via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based proliferation assays against the human colon carcinoma cell line HCT-116wt and the multidrug-resistant human breast carcinoma cell line MCF-7topo. Most complexes showed good cytotoxicity with IC50 values in the low micromolar range, while excellent sub-micromolar activity was observed for 2c, 3a and 3b. Generally, the activity of the ligands studied was as follows: carbene > phosphine > alkyne > halide, with an exception for the highly active iodido derivative 2c.

Keywords: Lepidiline A; N-heterocyclic carbene; anticancer drug; aurophilic interactions; cytotoxicity; gold.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Female
  • Gold / chemistry*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Models, Molecular
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Heterocyclic Compounds
  • Gold