Insight into the Anticancer Activity of Copper(II) 5-Methylenetrimethylammonium-Thiosemicarbazonates and Their Interaction with Organic Cation Transporters
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Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Strasse 42, A-1090 Vienna, Austria
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Department of Chemistry, Moldova State University, A. Mateevici Street 60, MD-2009 Chisinau, Moldova
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Petru Poni Institute of Macromolecular Chemistry, Laboratory of Inorganic Polymers, Aleea Grigore Ghica Voda, Nr. 41A, 700487 Iasi, Romania
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Elettra—Sincrotrone Trieste S.C.p.A, Strada Statale 14—km 163,5 in AREA Science Park, 34149 Basovizza, Trieste, Italy
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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
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Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
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MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
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Department of Medical Microbiology and Immunobiology, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary
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Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria
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Institute of Pharmacology, Centre for Physiology and Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria
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Neuroproteomics, Paracelsus Private Medical University, 5020 Salzburg, Austria
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Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(9), 1213; https://doi.org/10.3390/biom10091213
Received: 28 July 2020 / Revised: 13 August 2020 / Accepted: 14 August 2020 / Published: 20 August 2020
(This article belongs to the Special Issue 2020 Feature Papers by Biomolecules’ Editorial Board Members)
A series of four water-soluble salicylaldehyde thiosemicarbazones with a positively charged trimethylammonium moiety ([H2LR]Cl, R = H, Me, Et, Ph) and four copper(II) complexes [Cu(HLR)Cl]Cl (1–4) were synthesised with the aim to study (i) their antiproliferative activity in cancer cells and, (ii) for the first time for thiosemicarbazones, the interaction with membrane transport proteins, specifically organic cation transporters OCT1–3. The compounds were comprehensively characterised by analytical, spectroscopic and X-ray diffraction methods. The highest cytotoxic effect was observed in the neuroblastoma cell line SH-5YSY after 24 h exposure and follows the rank order: 3 > 2 > 4 > cisplatin > 1 >> [H2LR]Cl. The copper(II) complexes showed marked interaction with OCT1–3, comparable to that of well-known OCT inhibitors (decynium 22, prazosin and corticosterone) in the cell-based radiotracer uptake assays. The work paves the way for the development of more potent and selective anticancer drugs and/or OCT inhibitors.