Revisiting the thiosemicarbazonecopper(II) reaction with glutathione. Activity against colorectal carcinoma cell lines

Thiosemicarbazones (TSCs), and their copper derivatives, have been extensively studied mainly due to the potential applications as antitumor compounds. A part of the biological activity of the TSC-CuII complexes rests on their reactivity against cell reductants, as glutathione (GSH). The present paper describes the structure of the [Cu(PTSC)(ONO2)]n compound (1) (HPTSC=pyridine-2-carbaldehyde thiosemicarbazone) and its spectroscopic and magnetic properties. ESI studies performed on the reaction of GSH with 1 and the analogous [{Cu(PTSC*)(ONO2)}2] derivative (2, HPTSC*=pyridine-2-carbaldehyde 4N-methylthiosemicarbazone) show the absence of peaks related with TSC-Cu-GSH species. However GSH-Cu ones are detected, in good agreement with the release of CuI ions after reduction in the experimental conditions. The reactivity of 1 and 2 with cytochrome c and myoglobin and their activities against HT-29 and SW-480 colon carcinoma cell lines are compared with those shown by the free HPTSC and HPTSC* ligands. [Cu(PTSC)(ONO2)]n (1) exhibits a 2D crystal structure and antiferromagnetic interactions. 1 and [{Cu(PTSC*)(ONO2)}2] (2) react with glutathione, but no presence Cu-thiosemicarbazone-glutathione species is found. No marked interaction with cytochrome c and myoglobin is observed. 1 and 2 are cytotoxic against colon carcinoma cells, increase ROS levels and protein oxidation. [Display omitted] •[Cu(PTSC)(ONO2)]n (1) is 2D structure and antiferromagnetic.•PTSC− in 1 is tetradentate, with two hydrazinic nitrogens involved in bonding.•No ternary Cu-thiosemicarbazone-glutathione species are found.•No marked interaction with cytochrome c and myoglobin is observed.•1 and [{Cu(PTSC*)(ONO2)}2] show a cytotoxic effect on colon carcinoma cells.