Synthesis of N‐Aryl‐ and N‐alkyl‐Substituted Imidazolium Silver Complexes: Cytotoxic Screening by Using Human Cell Lines Modelling Acute Myeloid Leukaemia. (9th July 2020)

• Record Type: Journal Article
• Authors: Alme, Eirin; Törnroos, Karl Wilhelm; Gjertsen, Bjørn Tore; Bjørsvik, Hans‐René
• Is Part Of: ChemMedChem. Volume 15:Number 16(2020)
• Page Start: 1509
• Page End: 1514
• Publication Date: 2020-07-09
• Subjects: cytotoxicity -- leukaemia -- metallodrugs -- synthesis -- NHC-silver; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202000138
• Languages: English
• ISSNs: 1860-7179

Abstract

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. Abstract : Structure is paramount : Ag−N‐heterocyclic carbene complexes have been designed, synthesised, and biologically evaluated against human cell lines modelling acute myeloid leukaemia. The complexes were found to be cytotoxic at micromolar concentrations. Sterically demanding substituents on the N1 of the imidazole ring and an alkyl chain on N3 augmented the cytotoxicity.