{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:00:00Z","timestamp":1787655600832,"version":"build-2736575974"},"reference-count":88,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["(FWF grant no. P28223)"],"award-info":[{"award-number":["(FWF grant no. P28223)"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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\u20134) 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\u20133. 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 &gt; 2 &gt; 4 &gt; cisplatin &gt; 1 &gt;&gt; [H2LR]Cl. The copper(II) complexes showed marked interaction with OCT1\u20133, 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.<\/jats:p>","DOI":"10.3390\/biom10091213","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T09:35:31Z","timestamp":1597916131000},"page":"1213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Insight into the Anticancer Activity of Copper(II) 5-Methylenetrimethylammonium-Thiosemicarbazonates and Their Interaction with Organic Cation Transporters"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9012-2671","authenticated-orcid":false,"given":"Miljan N. M.","family":"Milunovi\u0107","sequence":"first","affiliation":[{"name":"Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, W\u00e4hringer Strasse 42, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8820-6411","authenticated-orcid":false,"given":"Oleg","family":"Palamarciuc","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Moldova State University, A. Mateevici Street 60, MD-2009 Chisinau, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3173-5176","authenticated-orcid":false,"given":"Angela","family":"Sirbu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Moldova State University, A. Mateevici Street 60, MD-2009 Chisinau, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1222-4373","authenticated-orcid":false,"given":"Sergiu","family":"Shova","sequence":"additional","affiliation":[{"name":"Petru Poni Institute of Macromolecular Chemistry, Laboratory of Inorganic Polymers, Aleea Grigore Ghica Voda, Nr. 41A, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-4870","authenticated-orcid":false,"given":"Dan","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Elettra\u2014Sincrotrone Trieste S.C.p.A, Strada Statale 14\u2014km 163,5 in AREA Science Park, 34149 Basovizza, Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Dvoranov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinsk\u00e9ho 9, SK-81237 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6071-3932","authenticated-orcid":false,"given":"Peter","family":"Rapta","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinsk\u00e9ho 9, SK-81237 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsiana V.","family":"Petrasheuskaya","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, D\u00f3m t\u00e9r 7, H-6720 Szeged, Hungary"},{"name":"MTA-SZTE Lend\u00fclet Functional Metal Complexes Research Group, University of Szeged, D\u00f3m t\u00e9r 7, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8058-8128","authenticated-orcid":false,"given":"Eva A.","family":"Enyedy","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, D\u00f3m t\u00e9r 7, H-6720 Szeged, Hungary"},{"name":"MTA-SZTE Lend\u00fclet Functional Metal Complexes Research Group, University of Szeged, D\u00f3m t\u00e9r 7, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8085-0950","authenticated-orcid":false,"given":"Gabriella","family":"Spengler","sequence":"additional","affiliation":[{"name":"MTA-SZTE Lend\u00fclet Functional Metal Complexes Research Group, University of Szeged, D\u00f3m t\u00e9r 7, H-6720 Szeged, Hungary"},{"name":"Department of Medical Microbiology and Immunobiology, University of Szeged, D\u00f3m t\u00e9r 10, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Ilic","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria"},{"name":"Institute of Pharmacology, Centre for Physiology and Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria"},{"name":"Neuroproteomics, Paracelsus Private Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-7444","authenticated-orcid":false,"given":"Harald H.","family":"Sitte","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Centre for Physiology and Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"Lubec","sequence":"additional","affiliation":[{"name":"Neuroproteomics, Paracelsus Private Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir B.","family":"Arion","sequence":"additional","affiliation":[{"name":"Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, W\u00e4hringer Strasse 42, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"ref_1","first-page":"167","article-title":"Observations on the antileukemic activity of pyridine-2-carboxaldehyde thiosemicarbazone and thiocarbohydrazone","volume":"16","author":"Brockman","year":"1956","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1021\/jm00300a025","article-title":"Carcinostatic activity of thiosemicarbazones of formyl heteroaromatic compounds. VII. 2-Formylpyridine derivatives bearing additional ring substituents","volume":"13","author":"French","year":"1970","journal-title":"J. Med. Chem."},{"key":"ref_3","first-page":"1692","article-title":"4-Methyl-5-amino-1-formylisoquinoline Thiosemicarbazone, a Second-Generation Antineoplastic Agent of the a-(N) Heterocyclic Carboxaldehyde Thiosemicarbazone Series","volume":"37","author":"Agrawal","year":"1977","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1021\/cr400135x","article-title":"Advances in Copper Complexes as Anticancer Agents","volume":"114","author":"Santini","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_5","unstructured":"(2020, July 26). Dose-finding and Pharmacokinetic Study of DpC, Administered Orally to Patients with Advanced Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02688101."},{"key":"ref_6","unstructured":"(2020, July 26). Study of COTI-2 as Monotherapy or Combination Therapy for the Treatment of Malignancies (COTI2-101), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02433626."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35768","DOI":"10.1074\/jbc.M112.396911","article-title":"Mechanistic Studies of Semicarbazone Triapine Targeting Human Ribonucleotide Reductase in Vitro and in Mammalian Cells: Tyrosyl Radical Quenching Not Involving Reactive Oxygen Species","volume":"287","author":"Aye","year":"2012","journal-title":"Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5271","DOI":"10.1021\/jm900552r","article-title":"Thiosemicarbazones from the Old to New: Iron Chelators That Are More Than Just Ribonucleotide Reductase Inhibitors","volume":"52","author":"Yu","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13045-016-0330-x","article-title":"The novel thiosemicarbazone, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), inhibits neuroblastoma growth in vitro and in vivo via multiple mechanisms","volume":"9","author":"Guo","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1021\/jm101532u","article-title":"Role of Metalation in the Topoisomerase II\u03b1 Inhibition and Antiproliferation Activity of a Series of \u03b1-Heterocyclic-N4-Substituted Thiosemicarbazones and Their Cu(II) Complexes","volume":"54","author":"Zeglis","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1089\/ars.2017.7487","article-title":"Anticancer Thiosemicarbazones: Chemical Properties, Interaction with Iron Metabolism, and Resistance Development","volume":"30","author":"Heffeter","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1039\/c0cs00215a","article-title":"Copper complexes of bis(thiosemicarbazones): From chemotherapeutics to diagnostic and therapeutic radiopharmaceuticals","volume":"40","author":"Paterson","year":"2011","journal-title":"Chem. Soc. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ejmech.2019.03.024","article-title":"Multi-target compounds acting in cancer progression: Focus on thiosemicarbazone, thiazole and thiazolidinone analogues","volume":"170","author":"Leite","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8478","DOI":"10.18632\/oncotarget.2328","article-title":"The Iron Chelator Dp44mT Inhibits Hepatocellular carcinoma Metastasis via N-Myc Downstream-regulated Gene 2 (NDRG2)\/gp130\/STAT3 Pathway","volume":"5","author":"Wang","year":"2014","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1182\/blood-2004-03-0868","article-title":"Novel Di-2-pyridyl-derived Iron Chelators with Marked and Selective Antitumor Activity: In vitro and in vivo Assessment","volume":"104","author":"Yuan","year":"2004","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1089\/ars.2012.4540","article-title":"Novel chelators for cancer treatment: Where are we now?","volume":"18","author":"Merlot","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Serda, M., Kalinowski, D.S., Rasko, N., Pot\u016f\u010dkov\u00e1, E., Mrozek-Wilczkiewicz, A., Musiol, R., Ma\u0142ecki, J.G., Sajewicz, M., Ratuszna, A., and Muchowicz, A. (2014). Exploring the Anti-Cancer Activity of Novel Thiosemicarbazones Generated through the Combination of Retro-Fragments: Dissection of Critical Structure-Activity Relationships. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110291"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6510","DOI":"10.1021\/jm0606342","article-title":"Dipyridyl Thiosemicarbazone Chelators with Potent and Selective Antitumor Activity Form Iron Complexes with Redox Activity","volume":"49","author":"Richardson","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.2174\/1874846501003020016","article-title":"Thiosemicarbazone Metal Complexes: From Structure to Activity","volume":"3","author":"Pelosi","year":"2010","journal-title":"Open Crystallogr. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jinorgbio.2017.11.009","article-title":"Effects of polar substituents on the biological activity of thiosemicarbazone metal complexes","volume":"179","author":"Bisceglie","year":"2018","journal-title":"Inorg. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9309","DOI":"10.1021\/ic300967j","article-title":"L- and D-Proline Thiosemicarbazone Conjugates: Coordination Behavior in Solution and the Effect of Copper(II) Coordination on Their Antiproliferative Activity","volume":"51","author":"Milunovic","year":"2012","journal-title":"Inorg. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13427","DOI":"10.1039\/C6DT02784A","article-title":"Structure\u2013antiproliferative Activity Studies on L-proline- and Homoproline-4-N-pyrrolidine-3-thiosemicarbazon Hybrids and Their Nickel(ii), Palladium(ii) and Copper(ii) Complexes","volume":"45","author":"Dobrova","year":"2016","journal-title":"Dalton Trans."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1021\/acs.inorgchem.6b03178","article-title":"New Iminodiacetate\u2013Thiosemicarbazone Hybrids and Their Copper(II) Complexes Are Potential Ribonucleotide Reductase R2 Inhibitors with High Antiproliferative Activity","volume":"56","author":"Zaltariov","year":"2017","journal-title":"Inorg. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1021\/acs.jmedchem.8b01031","article-title":"New Water-Soluble Copper(II) Complexes with Morpholine\u2013Thiosemicarbazone Hybrids: Insights into the Anticancer and Antibacterial Mode of Action","volume":"62","author":"Ohui","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1016\/j.bmc.2008.03.006","article-title":"Novel thiosemicarbazone derivatives as potential antitumor agents: Synthesis, physicochemical and structural properties, DNA interactions and antiproliferative activity","volume":"16","author":"Vrdoljak","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1007\/s11095-007-9254-z","article-title":"Polyspecific organic cation transporters: Structure, function, physiological roles, and biopharmaceutical implications","volume":"24","author":"Koepsell","year":"2007","journal-title":"Pharm. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1124\/pr.118.015578","article-title":"Organic Cation Transporters in Health and Disease","volume":"72","author":"Koepsell","year":"2020","journal-title":"Pharm. Rev."},{"key":"ref_28","unstructured":"Keogh, J., Hagenbuch, B., Rynn, C., Stieger, B., and Nicholls, G. (2016). Membrane Transporters: Fundamentals, Function and Their Role in ADME, Royal Society of Chemistry."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1080\/03602532.2018.1512614","article-title":"Subcellular drug distribution: Mechanisms and roles in drug efficacy, toxicity, resistance, and targeted delivery","volume":"50","author":"Li","year":"2018","journal-title":"Drug Metab. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8847","DOI":"10.1158\/0008-5472.CAN-06-0769","article-title":"Organic Cation Transporters Are Determinants of Oxaliplatin Cytotoxicity","volume":"66","author":"Zhang","year":"2006","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Taubert, D., Grimberg, G., Stenzel, W., and Sch\u00f6mig, E. (2007). Identification of the Endogenous Key Substrates of the Human Organic Cation Transporter OCT2 and Their Implication in Function of Dopaminergic Neurons. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000385"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/sj.bjp.0704785","article-title":"Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3","volume":"136","year":"2002","journal-title":"Br. J. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1124\/jpet.103.053298","article-title":"Pharmacological and Physiological Functions of the Polyspecific Organic Cation Transporters: OCT1, 2, and 3 (SLC22A1-3)","volume":"308","author":"Jonker","year":"2004","journal-title":"J. Pharm. Exp."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/j.bbamem.2015.04.001","article-title":"Functional characterization of the organic cation transporters (OCTs) in human airway pulmonary epithelial cells","volume":"1848","author":"Ingoglia","year":"2015","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fphar.2015.00085","article-title":"Role of transporters in the distribution of platinum-based drugs","volume":"6","author":"Harrach","year":"2015","journal-title":"Front. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1517\/17425255.2011.547474","article-title":"Role of organic cation transporters in drug-induced toxicity","volume":"7","author":"Ciarimboli","year":"2011","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1124\/mol.110.066126","article-title":"Membrane Transport and Intracellular Sequestration of Novel Thiosemicarbazone Chelators for the Treatment of Cancer","volume":"78","author":"Merlot","year":"2010","journal-title":"Mol. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9594","DOI":"10.1021\/ic201334q","article-title":"Mechanisms Controlling the Cellular Accumulation of Copper Bis(thiosemicarbazonato) Complexes","volume":"50","author":"Price","year":"2011","journal-title":"Inorg. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1021\/mp500114e","article-title":"Uptake of Compounds That Selectively Kill Multidrug-Resistant Cells: The Copper Transporter SLC31A1 (CTR1) Increases Cellular Accumulation of the Thiosemicarbazone NSC73306","volume":"11","author":"Fung","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9588","DOI":"10.1074\/jbc.M114.631283","article-title":"Di-2-pyridylketone 4,4-Dimethyl-3-thiosemicarbazone (Dp44mT) Overcomes Multidrug Resistance by a Novel Mechanism Involving the Hijacking of Lysosomal P-Glycoprotein (Pgp)","volume":"290","author":"Jansson","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1021\/ic402953s","article-title":"Acetylcholine-like and Trimethylglycine-like PTA (1,3,5-Triaza-7-phosphaadamantane) Derivatives for the Development of Innovative Ru- and Pt-Based Therapeutic Agents","volume":"53","author":"Ferretti","year":"2014","journal-title":"Inorg. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1021\/mp400024d","article-title":"Polyamine Transport by the Polyspecific Organic Cation Transporters OCT1, OCT2, and OCT3","volume":"10","author":"Li","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1246\/bcsj.70.615","article-title":"Synthesis of New Cationic Shiff Base Complexes of Copper(II) and Their Selective Binding with DNA","volume":"70","author":"Tanaka","year":"1997","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Leggett, D.J. (1985). Computational Methods for the Determination of Stability Constants, Plenum Press.","DOI":"10.1007\/978-1-4684-4934-1"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0003-2670(01)80616-4","article-title":"A Study of Some Problems in Determining the Stoicheiometric Proton Dissociation Constants of Complexes by Potentiometric Titrations Using a Glass Electrode","volume":"38","author":"Irving","year":"1967","journal-title":"Anal. Chim. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5895","DOI":"10.1039\/c0dt01835j","article-title":"Interaction of Triapine and Related Thiosemicarbazones with Iron(III)\/(II) and Gallium(III): A Comparative Solution Equilibrium Study","volume":"40","author":"Enyedy","year":"2011","journal-title":"Dalton Trans."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jinorgbio.2015.08.023","article-title":"Vanadium(IV\/V) Complexes of Triapine and Related Thiosemicarbazones: Synthesis, Solution Equilibrium and Bioactivity","volume":"152","author":"Kowol","year":"2015","journal-title":"J. Inorg. Biochem."},{"key":"ref_48","unstructured":"(2003). CrysAlis RED, Oxford Diffraction Ltd.. Version 1.171.40.53."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1107\/S0907444909047337","article-title":"XDS","volume":"66","author":"Kabsch","year":"2010","journal-title":"Acta Cryst. D Biol. Cryst."},{"key":"ref_50","first-page":"3","article-title":"Crystal structure refinement with SHELXL","volume":"C71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr."},{"key":"ref_51","first-page":"171","article-title":"The Cambridge Structural Database","volume":"B72","author":"Groom","year":"2016","journal-title":"Acta Cryst."},{"key":"ref_52","unstructured":"(2007). GraphPad Software I, Version 5.0, GraphPad Software Inc.. GraphPad Prism."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ejphar.2018.10.028","article-title":"Comparative analysis of novel decynium-22 analogs to inhibit transport by the low-affinity, high-capacity monoamine transporters, organic cation transporters 2 and 3, and plasma membrane monoamine transporter","volume":"842","author":"Basiouny","year":"2019","journal-title":"Eur. J. Pharm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1021\/acs.jmedchem.9b01938","article-title":"Structure\u2013Activity Relationships of Novel Thiazole-Based Modafinil Analogues Acting at Monoamine Transporters","volume":"63","author":"Kalaba","year":"2020","journal-title":"Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3833","DOI":"10.1039\/C7DT00283A","article-title":"Copper(II) thiosemicarbazone complexes induce marked ROS accumulation and promote nrf2-mediated antioxidant response in highly resistant breast cancer cells","volume":"46","author":"Palamarciuc","year":"2017","journal-title":"Dalton Trans."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5537","DOI":"10.1021\/ic062059y","article-title":"Cleavage of C\u2013S Bonds with the Formation of a Tetranuclear Cu(I) Cluster","volume":"46","author":"Huang","year":"2007","journal-title":"Inorg. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s11243-009-9322-9","article-title":"Synthesis, characterization and catalytic properties of heterogeneous iron(III) tetradentate Schiff base complexes for the aerobic epoxidation of styrene","volume":"35","author":"Yang","year":"2010","journal-title":"Transit. Met. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6739","DOI":"10.1021\/acs.jmedchem.6b00342","article-title":"Impact of Stepwise NH2-Methylation of Triapine on the Physicochemical Properties, Anticancer Activity, and Resistance Circumvention","volume":"59","author":"Kowol","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.1002\/ejic.201200360","article-title":"Complex-Formation Ability of Salicylaldehyde Thiosemicarbazone towards ZnII, CuII, FeII, FeIII and GaIII Ions","volume":"2012","author":"Enyedy","year":"2012","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1016\/0277-5387(95)00010-P","article-title":"Copper(II) Complexes of 2-Benzoylpyridine 4N-Substituted Thiosemicarbazones","volume":"14","author":"West","year":"1995","journal-title":"Polyhedrone"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1039\/C1DT11685A","article-title":"Biologically Active Thiosemicarbazone Fe Chelators and Their Reactions with Ferrioxamine B and Ferric EDTA; a Kinetic Study","volume":"41","author":"Bernhardt","year":"2012","journal-title":"Dalton Trans."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1016\/j.jinorgbio.2007.07.026","article-title":"Effect of Metal Ion Complexation and Chalcogen Donor Identity on the Antiproliferative Activity of 2-Acetylpyridine N,N-Dimethyl(chalcogen)semicarbazones","volume":"101","author":"Kowol","year":"2007","journal-title":"J. Inorg. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ica.2017.07.001","article-title":"A Comparative Study of \u03b1-N-pyridyl Thiosemicarbazones: Spectroscopic Properties, Solution Stability and Copper(II) Complexation","volume":"472","author":"May","year":"2018","journal-title":"Inorg. Chim. Acta"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1089\/ars.2019.7854","article-title":"High Copper Complex Stability and Slow Reduction Kinetics as Key Parameters for Improved Activity, Paraptosis Induction and Impact on Drug-resistant Cells of Anticancer Thiosemicarbazones","volume":"33","author":"Hager","year":"2020","journal-title":"Antioxid. Redox Signal."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1039\/C6MT00105J","article-title":"Copper and Conquer: Copper Complexes of Di-2-pyridylketone Thiosemicarbazones as Novel Anti-cancer Therapeutics","volume":"8","author":"Park","year":"2016","journal-title":"Metallomics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1089\/ars.2010.3663","article-title":"Anticancer Activity of Metal Complexes: Involvement of Redox Processes","volume":"15","author":"Jungwirth","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1039\/c9mt00061e","article-title":"Reactivity of Cu(II)\u2013, Zn(II)\u2013 and Fe(II)\u2013thiosemicarbazone Complexes with Glutathione and Metallothionein: From Stability to Dissociation to Transmetallation","volume":"11","author":"Santoro","year":"2019","journal-title":"Metallomics"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5270","DOI":"10.1021\/ja012668z","article-title":"An Unusual Dimeric Structure of a Cu(I) Bis(thiosemicarbazone) Complex: Implications for the Mechanism of Hypoxic Selectivity of the Cu(II) Derivatives","volume":"124","author":"Cowley","year":"2002","journal-title":"Am. Chem. Soc."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.poly.2012.08.014","article-title":"The Influence of Substituents (R) at N1 atom of Furan-2-carbaldehyde Thiosemicarbazones {(C4H3O)HC2N3\u2013N(H)\u2013C1(S)N1HR} on Bonding, Nuclearity, H-bonded Networks of Copper(I) Complexes","volume":"47","author":"Lobana","year":"2012","journal-title":"Polyhedron"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"32269","DOI":"10.1039\/C8RA06057F","article-title":"Role of C, S, Se and P donor ligands in copper(I) mediated C\u2013N and C\u2013Si bond formation reactions","volume":"8","author":"Srinivas","year":"2018","journal-title":"RSC Adv."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1021\/ic035451+","article-title":"Functionalized Thiosemicarbazone Clusters of Copper(I) and Silver(I)","volume":"43","author":"Ashfield","year":"2004","journal-title":"Inorg. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7100","DOI":"10.1002\/slct.201800934","article-title":"Bis(thiosemicarbazone)copper(I) Complexes as Prospective Therapeutic Agents: Interaction with DNA\/BSA Molecules, and In Vitro and In Vivo Anti-Proliferative Activities","volume":"3","author":"Mahendiran","year":"2018","journal-title":"ChemistrySelect"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5759","DOI":"10.1021\/jm100561b","article-title":"Novel Thiosemicarbazones of the ApT and DpT Series and Their Copper Complexes: Identification of Pronounced Redox Activity and Characterization of Their Antitumor Activity","volume":"53","author":"Jansson","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Casella, L., Gullotti, M., Pintar, A., Pinciroli, F., Vigan\u00f2, R., and Zanello, P.J. (1989). Blue copper models. Spectroscopic and electrochemical studies of copper(II) complexes with new ligand systems containing sulphur and nitrogen donor atoms. Chem. Soc. Dalton Trans., 1161\u20131169.","DOI":"10.1039\/DT9890001161"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1021\/ja002995r","article-title":"Direct Evidence for a Geometrically Constrained \u201cEntatic State\u201d Effect on Copper(II\/I) Electron-Transfer Kinetics As Manifested in Metastable Intermediates","volume":"123","author":"Yu","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1021\/ic000358w","article-title":"Cross-Electron-Transfer Reactions of the [CuII\/I(bite)]2+\/+ Redox Couple","volume":"40","author":"Xie","year":"2001","journal-title":"Inorg. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jelechem.2003.11.019","article-title":"ESR\/UV\u2013Vis\u2013NIR cyclovoltammetry of macrocyclic complex [CuI(bite)]BF4 at different temperatures","volume":"566","author":"Rapta","year":"2004","journal-title":"Electroanal. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7830","DOI":"10.1002\/anie.201916316","article-title":"The Glutathione\/Metallothionein System Challenges the Design of Efficient O2-Activating Copper Complexes","volume":"59","author":"Santoro","year":"2020","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant activity applying an improved ABTS radical cation decolorization assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1039\/C9MD00594C","article-title":"Isoquinoline thiosemicarbazone displays potent anticancer activity with in vivo efficacy against aggressive leukemias","volume":"11","author":"Sun","year":"2020","journal-title":"RSC Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10425","DOI":"10.1158\/0008-5472.CAN-06-2126","article-title":"Disulfiram, a Clinically Used Anti-Alcoholism Drug and Copper-Binding Agent, Induces Apoptotic Cell Death in Breast Cancer Cultures and Xenografts via Inhibition of the Proteasome Activity","volume":"66","author":"Chen","year":"2006","journal-title":"Cancer Res."},{"key":"ref_82","first-page":"1","article-title":"Treatment of Metastatic Cancer with Tetrathiomolybdate, an Anticopper, Antiangiogenic Agent: Phase I Study","volume":"6","author":"Brewer","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"14901","DOI":"10.1073\/pnas.0604979103","article-title":"A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics","volume":"103","author":"Whitnall","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.chembiol.2018.02.010","article-title":"Copper-Binding Small Molecule Induces Oxidative Stress and Cell-Cycle Arrest in Glioblastoma-Patient-Derived Cells","volume":"25","author":"Shimada","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1023\/A:1025032511040","article-title":"pH-Dependent Bidirectional Transport of Weakly Basic Drugs Across Caco-2 Monolayers: Implications for Drug\u2013Drug Interactions","volume":"20","author":"Neuhoff","year":"2003","journal-title":"Pharm. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.phrs.2016.06.002","article-title":"Polyspecific organic cation transporters and their impact on drug intracellular levels and pharmacodynamics","volume":"111","author":"Wagner","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1124\/mol.105.016832","article-title":"Interaction of Organic Cations with a Newly Identified Plasma Membrane Monoamine Transporter","volume":"68","author":"Engel","year":"2005","journal-title":"Mol. Pharm."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1038\/s41386-018-0053-5","article-title":"An unsuspected role for organic cation transporter 3 in the actions of amphetamine","volume":"43","author":"Mayer","year":"2018","journal-title":"Neuropsychopharmacology"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/9\/1213\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:04:15Z","timestamp":1760177055000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/9\/1213"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,20]]},"references-count":88,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["biom10091213"],"URL":"https:\/\/doi.org\/10.3390\/biom10091213","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,20]]}}}