Synthesis and anticancer activity of silver(i)–N-heterocyclic carbene complexes derived from the natural xanthine products caffeine, theophylline and theobromine

Abstract

A new library of silver(I)-N-heterocyclic carbene complexes prepared from the natural products caffeine, theophylline and theobromine is reported. The complexes have been fully characterised using a combination of NMR spectroscopy, mass spectrometry, elemental analysis and X-ray diffraction analysis. Furthermore, the hydrophobicity of the complexes has been measured. The silver(I)-N-heterocyclic carbenes have been evaluated for their antiproliferative properties against a range of cancer cell lines of different histological types, and compared to cisplatin. The data shows different profiles of response when compared to cisplatin in the same panel of cells, indicating a different mechanism of action. Furthermore, it appears that the steric effect of the ligand and the hydrophobicity of the complex both play a role in the chemosensitivity of these compounds, with greater steric bulk and greater hydrophilicity delivering higher cytotoxicity.

Silver coordination compounds: A new horizon in medicine

“…2, 7) derived from natural xanthines (caffeine, theophylline and theobromine) gave different response profiles when compared to cisplatin in the same panel of cells, evidencing a different mechanism of action with respect to the reference compound. Furthermore, it appears that the steric effect of the ligand and the hydrophobicity of the complex both play a role in the chemosensitivity of these compounds, with greater steric bulk and greater hydrophilicity causing higher cytotoxicity [57].…”

Plants to Polyelectrolytes: Theophylline Polymers and Their Microsphere Synthesis

“…Quenching of the residual NaH and precipitation of the hydrophobic product occurred simultaneously upon addition of the mixture to water, followed by an MeOH rinse to isolate the pure product 1 . We initially tried to quaternize 1 with methyl iodide, as reported for similar compounds like caffeine . However the harsh reaction conditions required (>70 °C, 24 h) resulted in undesired side reactions (Figure S4, Supporting Information).…”

Silver carbene complexes: An emerging class of anticancer agents

“…A recent library of SCCs ( 32a ‐ e ) was complexed with natural products such as caffeine, theophylline, and theobromine (Figure ) (Mohamed, Lake, Laing, Phillips, & Willans, ). In this study, SCCs were evaluated for their antiproliferative activity in comparison to cisplatin against eight cancer cell lines of different origin.…”