| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1317851 | Journal of Inorganic Biochemistry | 2012 | 7 Pages |
Five new heterocyclic gold carbene complexes were prepared, four chlorido-[1,3-dimethyl-4,5-diarylimidazol-2-ylidene]gold complexes 6a-d and a chlorido-[1,3-dibenzylimidazol-2-ylidene]gold complex 11, and three of them were characterised by X-ray single crystal analyses. They were tested for cytotoxicity against a panel of four human cancer cell lines and non-malignant fibroblasts, for tubulin interaction, and for the pathways of their uptake into 518A2 melanoma cells. All complexes showed cytotoxic activity in the micromolar IC50 range with distinct selectivities for certain cell lines. In stark contrast to related metal-free 1-methyl-4,5-diarylimidazoles, the complexes 6 and 11 did not noticeably inhibit the polymerisation of tubulin to give microtubules. The cellular uptake of complexes 6 occurred mainly via the copper transporter (Ctr1) and the organic cation transporters (OCT-1/2). Complex 11 was accumulated preferentially via the organic cation transporters and by Na+/K+-dependent endocytosis. The new gold carbene complexes seem to operate by a mechanism different from that of the parent 1-methylimidazolium ligands.
Graphical abstractThe cellular uptake, cytotoxicity and cancer selectivity of new gold(I) N-heterocyclic carbene complexes of diarylimidazoles depend on the substituents and position of the arenes. For instance, complex 6c was most efficacious against HL-60 leukemia and was taken up mainly via organic cation transporters and the copper transporter.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Gold(I) N-heterocyclic carbene complexes of diarylimidazoles were prepared. ► They differ from the parent imidazoles in mode of cellular uptake and anticancer action. ► The substitution pattern of the imidazole is decisive for activity and specificity. ► Tubulin binding and anticancer effect are not correlated for the new complexes. ► The residues on the aryl rings allow a fine-tuning of anticancer efficacy.
