Synthesis and cytotoxicity studies of p-benzyl substituted NHC–copper(I) bromide derivatives

Two series of newly synthesised N-heterocyclic carbene–copper(I) bromide derivatives (1a–e and 2a–e) have been isolated and characterised.A series of highly biologically active symmetrically and un-symmetrically p-benzyl substituted imidazolium halides, reported previously by our group, was chosen as precursors for the series 2a–e.The imidazolium halides were reacted with silver oxide and then transmetallated to copper(I) to yield the corresponding N-heterocyclic carbene (NHC) copper(I) bromide complexes.The NHC–copper(I) bromide complexes 1a–e were found to be cytotoxic, giving IC50 values of 3.8 (±0.9), 7.4 (±2.4), 0.60 (±0.09), 13 (±4) and 42 (±7) μM, while NHC–copper(I) bromide complexes 2a–e showed IC50 values of 17 (±2), 21 (±3), 26 (±5), 68 (±7) and 61 (±10) μM against the breast cancer cell line MCF-7, respectively.The same NHC–copper(I) complexes 1a–e exhibited IC50 values of 5.6 (±0.9), 3.3 (±0.6), 0.65 (±0.08), 18 (±3) and 126 (±10) μM, while NHC–copper(I) bromide complexes 2a–e gave IC50 values of 17 (±2), 19 (±1), 18 (±1), 47 (±3) and 134 (±16) μM against the renal cancer cell-line Caki-1, respectively.

Graphical abstractTen novel N-heterocyclic carbene–copper(I) bromide derivatives were synthesised, chemically characterised and biologically evaluated against two human cancer cell lines, where the best compound showed nanomolar activity.Figure optionsDownload full-size imageDownload as PowerPoint slide