Synthesis, cytotoxic and antibacterial studies of p-benzyl-substituted NHC–silver(I) acetate compounds derived from 4,5-di-p-diisopropylphenyl- or 4,5-di-p-chlorophenyl-1H-imidazole

Abstract

4,5-Di(p-isopropylphenyl)-1H-imidazole (2a) and 4,5-di(p-chlorophenyl)-1H-imidazole (2b) were prepared from the appropriately substituted benzoin precursors and then reacted with five p-substituted benzyl halide derivatives through N-dibenzylation to the symmetrically (3a–j) or through N-monobenzylation followed by N-methylation to the un-symmetrically substituted (5b) imidazolium halides. These halides were further used for the synthesis of the corresponding N-heterocyclic carbene–silver(I) (NHC–silver) acetate complexes 4a–j and 5c. The silver(I) compounds 4b, 4e and 4g were characterised by single crystal X-ray diffraction.Semiquantitative antibacterial studies against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus, using the Kirby–Bauer disc diffusion method, were carried out on the imidazolium halides 3a–j and NHC–silver(I) acetate complexes 4a–g and 4i–j. Imidazolium halide precursors 3a–j showed bacterial growth inhibition in the range of 1–5 mm (weak) while their NHC–silver(I) acetate derivatives 4a–g and 4i–j were found to inhibit bacterial growth in range 2–6 mm (weak to medium).The NHC–silver(I) acetate complexes 4a–g and 4i–j were found to be cytotoxic by producing IC50 values of 4.7 (±0.5), 2.1 (±0.8), 3.4 (±0.6), 15 (±2), 25 (±7), 24 (±3), 14 (±3), 21 (±5) and 50 (±2) μM against the breast cancer cell line MCF-7, respectively. The same NHC–silver(I) complexes 4a–g and 4i–j exhibited IC50 values of 8.7 (±1.5), 4.6 (±0.6), 5.5 (±0.6), 34 (±1), 42 (±4), 44 (±3), 29 (±1), 100 (±2) and 140 (±10) μM against the renal cancer cell-line Caki-1, respectively. The un-symmetrically substituted compound 5c has IC50 values of 24 (±3) μM against MCF-7 and 44 (±3) μM against Caki-1.