NHC-Silver(I) Acetates as Bioorganometallic Anticancer and Antibacterial Drugs

The synthesis of N-heterocyclic carbene (NHC) silver(I) acetate complexes with varying lipophilic benzyl-substituents at the 1 and 3 positions of the (benz)imidazole ring was achieved by reaction of silver(I) acetate with the corresponding (benz)imidazolium bromide or iodide salts. These NHC-silver(I) acetate derivatives exhibit interesting structural motifs in the solid state and proof to be soluble and stable in biological media. The preliminary antibacterial activity of all the compounds was studied against Gram-negative bacteria Escherichia coli, and Gram-positive bacteria Staphylococcus aureus using the Kirby-Bauer disk-diffusion method. Almost all the NHC-silver(I) acetate complexes have shown high antibacterial activity compared to the NHC-precursors. In addition, the NHC-silver complexes had their cytotoxicity investigated through MTT based preliminary in vitro testing on the human renal cancer cell line Caki-1 in order to determine their IC50 values. NHC-silver(I) acetate complexes were found to have IC50 values ranging from 1.2 to 63 M. These values represent improved cytotoxicity against Caki-1, most notably for (1-methyl-3-(4-cyanobenzyl) benzimidazole-2-ylidene) silver(I) acetate (IC50 value = 1.2 M), which is a three times more cytotoxic than cisplatin exhibiting an IC50 value of 3.3 M against this cell line.