Reactivity towards DNA and protein, cellular uptake, cytotoxic activity of a mononuclear copper(II) complex of the thioflavin-T (ThT)-based derivative

DNA- and protein-binding properties, cellular uptake, and cytotoxicity activity of a mononuclear copper(II) complex, [CuLCl2] (1, whereL = 4 '-bis(pyridine-2-ylmethyl)amiono-2-phenylbenzothiazole), were investigated. The results show that1can effectively enter the cancer cells, even the nucleus, and exhibit cytotoxicity comparable to that of cisplatin against A549 and MCF-7 cell lines. Complex1could strongly bind to calf-thymus DNA (CT-DNA) mainly by intercalation mode and induce a remarkable conformational variation of DNA. The intrinsic binding constantK(b)of1to DNA is 4.15 x 10(5)M(-1)and the apparent binding constantK(app)is 1.25 x 10(6)M(-1). Agarose gel electrophoresis revealed that1could efficiently cleave the supercoiled pBR322 DNA into its nicked and linear forms in the presence of excessive H2O2. The evaluation of the protein binding ability showed that1could also bind to human serum albumin (HSA) with a moderate binding affinity, quench the intrinsic fluorescence of HSA, and induce the conformational change of the protein.