Synthesis of N-Aryl- and N-alkyl-Substituted Imidazolium Silver Complexes: Cytotoxic Screening by Using Human Cell Lines Modelling Acute Myeloid Leukaemia

ChemMedChem. 2020 Aug 19;15(16):1509-1514. doi: 10.1002/cmdc.202000138. Epub 2020 Jul 9.

Abstract

A series of N-aryl- and N-alkyl substituted imidazoles has been synthesised and complexed with Ag+ to obtain silver-NHC complexes of the form [Ag(NHC)2 ]X. These silver-NHC complexes were tested in vitro against the human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). A substantial difference in cytotoxicity was revealed varying in the range 13-4 μM and 22-9 μM for HL-60 and MOLM-13, respectively. Furthermore, this study revealed that when an alkyl group is installed on the imidazole scaffold, its position substantially influences the cytotoxicity of the corresponding silver NHC complex.

Keywords: NHC-silver; cytotoxicity; leukaemia; metallodrugs; synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Drug Screening Assays, Antitumor
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology
  • Models, Biological*
  • Molecular Structure
  • Silver / chemistry
  • Silver / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Imidazoles
  • Silver
  • imidazole