title: Copper(ii) thiosemicarbazone complexes induce marked ROS accumulation and promote nrf2-mediated antioxidant response in highly resistant breast cancer cells.
abstract: A series of water-soluble sodium salts of 3-formyl-4-hydroxybenzenesulfonic acid thiosemicarbazones (or sodium 5-sulfonate-salicylaldehyde thiosemicarbazones) containing different substituents at the terminal nitrogen atom (H, Me, Et, Ph) and their copper(ii) complexes have been prepared and characterised by elemental analysis, spectroscopic techniques (IR, UV-vis,1H NMR), ESI mass spectrometry, X-ray crystallography and cyclic voltammetry. The proligands and their copper(ii) complexes exhibit moderate water solubility and good stability in aqueous environment, determined by investigating their proton dissociation and complex formation equilibria. The copper(ii) complexes showed moderate anticancer activity in established human cancer cell lines, while the proligands were devoid of cytotoxicity. The anticancer activity of the copper(ii) complexes correlates with their ability to induce ROS accumulation in cells, consistent with their redox potentials within the biological window, triggering the activation of antioxidation defense mechanisms in response to the ROS insult. These studies pave the way for the investigation of ROS-inducing copper(ii) complexes as prospective antiproliferative agents in cancer chemotherapy.
authors.affiliation: Moldova State University, Department of Chemistry, A. Mateevici Street 60, MD-2009, Chisinau, Republic of Moldova.
authors.forename: Angela
authors.initials: A
authors.lastname: Sîrbu
authors.affiliation: Moldova State University, Department of Chemistry, A. Mateevici Street 60, MD-2009, Chisinau, Republic of Moldova.
authors.forename: Oleg
authors.initials: O
authors.lastname: Palamarciuc
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 2, 117543 Singapore. chmawh@nus.edu.sg phamari@nus.edu.sg.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Babak
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 2, 117543 Singapore. chmawh@nus.edu.sg phamari@nus.edu.sg.
authors.forename: Jia Min
authors.initials: JM
authors.lastname: Lim
authors.affiliation: Institute of Inorganic Chemistry of the University of Vienna, Währinger Strasse 42, A-1090 Vienna, Austria. vladimir.arion@univie.ac.at.
authors.forename: Kateryna
authors.initials: K
authors.lastname: Ohui
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7., H-6720 Szeged, Hungary.
authors.forename: Eva A
authors.initials: EA
authors.lastname: Enyedy
authors.affiliation: Petru Poni Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda, Nr. 41A, 700487 Iasi, Romania.
authors.forename: Sergiu
authors.initials: S
authors.lastname: Shova
authors.affiliation: Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-81237 Bratislava, Slovakia.
authors.forename: Denisa
authors.initials: D
authors.lastname: Darvasiová
authors.affiliation: Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-81237 Bratislava, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Rapta
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 2, 117543 Singapore. chmawh@nus.edu.sg phamari@nus.edu.sg.
authors.forename: Wee Han
authors.identifier: http://orcid.org/0000-0003-2027-356X
authors.initials: WH
authors.lastname: Ang
authors.affiliation: Institute of Inorganic Chemistry of the University of Vienna, Währinger Strasse 42, A-1090 Vienna, Austria. vladimir.arion@univie.ac.at.
authors.forename: Vladimir B
authors.identifier: http://orcid.org/0000-0002-1895-6460
authors.initials: VB
authors.lastname: Arion
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004563:Electrochemistry; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013882:Thiosemicarbazones / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D013882:Thiosemicarbazones; D014867:Water; D003300:Copper