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

J Inorg Biochem. 2018 Mar:180:69-79. doi: 10.1016/j.jinorgbio.2017.12.005. Epub 2017 Dec 8.

Abstract

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.

Keywords: Colon carcinoma; Copper; Molecular magnetism; Thiosemicarbazone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Copper / chemistry*
  • Crystallography, X-Ray
  • Cytochromes c / metabolism
  • Drug Screening Assays, Antitumor
  • Glutathione / chemistry*
  • Glutathione / metabolism
  • Humans
  • Molecular Structure
  • Myoglobin / metabolism
  • Spectrometry, Mass, Electrospray Ionization
  • Spectroscopy, Fourier Transform Infrared
  • Thiosemicarbazones / chemistry*
  • Thiosemicarbazones / pharmacology*

Substances

  • Myoglobin
  • Thiosemicarbazones
  • Copper
  • Cytochromes c
  • Glutathione