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A series of novel (C^N) cyclometallated Au(III) complexes of general formula [Au(py(b)-H)L(1)L(2)](n+) (py(b)-H = C^N cyclometallated 2-benzylpyridine, L(1) and L(2) being chlorido, phosphane or glucosethiolato ligands, n = 0 or 1) have been synthesized and fully characterized using different techniques, including NMR, IR and far-IR, mass spectrometry, as well as elemental analysis. The crystal structure of one compound has been solved using X-ray diffraction methods. All compounds were tested in vitro in five human cancer cell lines including the lung, breast, colon and ovarian cancer cells. For comparison purposes, all compounds were also tested in a model of healthy human cells from the embryonic kidney. Notably, all new compounds were more toxic than their cyclometallated precursor bearing two chlorido ligands, and the derivative bearing one phosphane ligand presented the most promising toxicity profile in our in vitro screening, displaying a p53 dependent activity in colorectal cancer HCT116 cells. Finally, for the first time C^N cyclometallated gold(III) complexes were shown to be potent inhibitors of the zinc finger protein PARP-1, involved in the mechanism of cisplatin resistance.

Exploring the potential of gold(iii) cyclometallated compounds as cytotoxic agents: variations on the C^N theme