Novel multicharged silver(I)–NHC complexes derived from zwitterionic 1,3-symmetrically and 1,3-unsymmetrically substituted imidazoles and benzimidazoles: Synthesis and cytotoxic properties

Novel zwitterionic N-heterocyclic carbenes (NHCs) precursors, 1,3-symmetrically substituted NaHIm(1R,3R,4R '') (R = (CH2)(3)SO(3) over bar, R '' = H or CH3), NaHBzim(1R,3R) (R = (CH2)(3)SO(3) over bar), and 1,3-unsymmetrically substituted NaHIm(1R,3R',4R '') (R = (CH2)(3)SO(3) over bar, R' = CH2C6H5, R '' = H or CH3), [HBzim(1R,3R')]Br (R = (CH2)(3)SO3Na, R' = R or CH2C6H5) have been synthesized and used in the synthesis of multicharged silver(I)-NHC complexes. These compounds have been characterized using IR and NMR spectroscopy and by electrospray mass spectrometry. The N-heterocyclic carbene ligand precursor Him(1) and the intermediate HBzim(PrSO3) were also characterized by X-ray crystallography. Silver(I)-NHCs and the corresponding silver free ligands were assayed for their cytotoxic properties against a panel of human tumour cell lines including lung (A549), colon (HCT-15), breast (MCF-7) and cervical (A431) cancers, along with melanoma (A375). Their antiproliferative activity was further investigated on a human ovarian cell line pair which has been selected for sensitivity/resistance to cisplatin, i.e. 2008/C13* cancer cells. All complexes elicited a similar cytotoxic profile both in cisplatin-sensitive and -resistant cell lines, with resistance factors (R.F.) up to 9 times lower than that of cisplatin, attesting the ability of these derivatives to overcome acquired cisplatin resistance.