A new class of highly cytotoxic luminescent platinum(II) complexes containing C^N^N moiety were prepared. These complexes are stable in physiological conditions, and have unexpected high anti-proliferation activities towards cancers with IC50 values down to nanomolar range, and are much more potent than the clinically used Topoisomerase I (TopoI) poison camptothecin (CPT) in killing cancer cells. Importantly, these complexes show relatively low potency toward normal human cell. [PtII(C^N^N)(C=NR)](ClO4) 1c (HC^N^N = 6-aryl-2,2'-bipyridine; R = tert-butyl) binds DNA through intercalative mode with a binding constant 1.0�106 mol�1 dm3, accompanied by up to 175-fold increase in the intensity of photoluminescence at lmax = 620 nm. The strong and selective binding of 1c toward DNA may account for its highly cytotoxic in killing human cancer cells. The cell death pathway is, at least in part, by stabilizing the TopoI-linked DNA via intercalation resulting in topoisomerase poisoning, which triggers DNA damage leading to apoptosis.

Platinum(II) complexes as a new class of topoisomerase I poisons

239th National Meeting (2010)

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