The first water-soluble copper(I) complexes bearing sulfonated imidazole- and benzimidazole-derived N-heterocyclic carbenes: Synthesis and anticancer studies

The first water-soluble bis(NHCSO3)CuCl complexes (NHCSO3 = NaImBn,PrSO3, Na2(4-Me)ImPrSO3 and Na2BzImPrSO3) derived from the sulfonated N-heterocyclic carbene precursors HImBn,PrSO3 (3-(1-benzyl-1H-imidazol-3-ium-3-yl)propane-1-sulfonate), Na(4-Me)HImPrSO3 (sodium 3,3′-(4-methyl-1H-imidazole-3-ium-1,3-diyl)dipropane-1-sulfonate) and NaHBzImPrSO3 (sodium 3,3′-(1H-benzoimidazole-3-ium-1,3-diyl)dipropane-1-sulfonate) have been synthesized. These compounds have been characterized using infrared and NMR spectroscopy and electrospray ionization mass spectrometry. The in vitro anti-tumour effects of the bis(NHCSO3)CuCl complexes and the corresponding free ligands were evaluated for a panel of various human tumour cell lines, including examples of lung, colon, ovarian and cervical carcinoma as well as of melanoma. Their cytotoxic properties were also evaluated against non-transformed human cells and on a cellular model of cisplatin resistance. NHC-copper complexes induced cell killing effects preferentially against tumour cells, with IC50 values in the micromolar range. Additionally, they were found able to overcome acquired cisplatin resistance.