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 NHC ligands precursors were prepared.
• Multicharged silver(I)-NHC complexes were synthesized.
• The new compounds were assayed for their cytotoxic properties against a panel of human tumor cell lines.

Novel zwitterionic N-heterocyclic carbenes (NHCs) precursors, 1,3-symmetrically substituted NaHIm1R,3R,4R″ (R = (CH2)3SO3−, R″ = H or CH3), NaHBzim1R,3R (R = (CH2)3SO3−), and 1,3-unsymmetrically substituted NaHIm1R,3R′,4R″ (R = (CH2)3SO3−, R′ = CH2C6H5, R″ = H or CH3), [HBzim1R,3R′]Br (R = (CH2)3SO3Na, 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 Him1 and the intermediate HBzimPrSO3 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.

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