{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T20:23:59Z","timestamp":1773865439285,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T00:00:00Z","timestamp":1600473600000},"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":["P28223-N34"],"award-info":[{"award-number":["P28223-N34"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Thiosemicarbazones continue to attract the interest of researchers as potential anticancer drugs. For example, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, or triapine, is the most well-known representative of this class of compounds that has entered multiple phase I and II clinical trials. Two new triapine derivatives HL1 and HL2 were prepared by condensation reactions of 2-pyridinamidrazone and S-methylisothiosemicarbazidium chloride with 3-N-(tert-butyloxycarbonyl) amino-pyridine-2-carboxaldehyde, followed by a Boc-deprotection procedure. Subsequent reaction of HL1 and HL2 with CuCl2\u00b72H2O in 1:1 molar ratio in methanol produced the complexes [CuII(HL1)Cl2]\u00b7H2O (1\u00b7H2O) and [CuII(HL2)Cl2] (2). The reaction of HL2 with Fe(NO3)3\u22199H2O in 2:1 molar ratio in the presence of triethylamine afforded the complex [FeIII(L2)2]NO3\u22190.75H2O (3\u22190.75H2O), in which the isothiosemicarbazone acts as a tridentate monoanionic ligand. The crystal structures of HL1, HL2 and metal complexes 1 and 2 were determined by single crystal X-ray diffraction. The UV-Vis and EPR spectroelectrochemical measurements revealed that complexes 1 and 2 underwent irreversible reduction of Cu(II) with subsequent ligand release, while 3 showed an almost reversible electrochemical reduction in dimethyl sulfoxide (DMSO). Aqueous solution behaviour of HL1 and 1, as well as of HL2 and its complex 2, was monitored as well. Complexes 1\u22123 were tested against ovarian carcinoma cells, as well as noncancerous embryonic kidney cells, in comparison to respective free ligands, triapine and cisplatin. While the free ligands HL1 and HL2 were devoid of antiproliferative activity, their respective metal complexes showed remarkable antiproliferative activity in a micromolar concentration range. The activity was not related to the inhibition of ribonucleotide reductase (RNR) R2 protein, but rather to cancer cell homeostasis disturbance\u2014leading to the disruption of cancer cell signalling.<\/jats:p>","DOI":"10.3390\/biom10091336","type":"journal-article","created":{"date-parts":[[2020,9,19]],"date-time":"2020-09-19T07:06:09Z","timestamp":1600499169000},"page":"1336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Triapine Derivatives Act as Copper Delivery Vehicles to Induce Deadly Metal Overload in Cancer Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Kateryna","family":"Ohui","sequence":"first","affiliation":[{"name":"Institute of Inorganic Chemistry, University of Vienna, W\u00e4hringer Strasse 42, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iryna","family":"Stepanenko","sequence":"additional","affiliation":[{"name":"Institute of Inorganic Chemistry, University of Vienna, W\u00e4hringer Strasse 42, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iuliana","family":"Besleaga","sequence":"additional","affiliation":[{"name":"Institute of Inorganic Chemistry, University of Vienna, W\u00e4hringer Strasse 42, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2009-7837","authenticated-orcid":false,"given":"Maria V.","family":"Babak","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National University of Singapore, 3 Science Drive 2, Singapore 117543, Singapore"},{"name":"Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong SAR 999077, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radu","family":"Stafi","sequence":"additional","affiliation":[{"name":"Institute of Inorganic Chemistry, University of Vienna, W\u00e4hringer Strasse 42, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denisa","family":"Darvasiova","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry and Chemical Physics, Slovak University of Technology in Bratislava, Radlinsk\u00e9ho 9, SK-81237 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald","family":"Giester","sequence":"additional","affiliation":[{"name":"Department of Mineralogy and Crystallography, University of Vienna, Althan Strasse 14, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivien","family":"P\u00f3sa","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Vegh","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Catalysis and Petrochemistry, Department of Organic Chemistry, Slovak University of Technology in Bratislava, Radlinsk\u00e9ho 9, SK-81237 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Slovak University of Technology in Bratislava, Radlinsk\u00e9ho 9, SK-81237 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wee Han","family":"Ang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National University of Singapore, 3 Science Drive 2, Singapore 117543, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-2391","authenticated-orcid":false,"given":"Ana","family":"Popovi\u0107-Bijeli\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Physical Chemistry, University of Belgrade, 11158 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir B.","family":"Arion","sequence":"additional","affiliation":[{"name":"Institute of Inorganic Chemistry, University of Vienna, W\u00e4hringer Strasse 42, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,19]]},"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":"201","DOI":"10.1007\/s00280-016-3200-x","article-title":"Phase I Trial of Daily Triapine in Combination with Cisplatin Chemotherapy for Advanced-Stage Malignancies","volume":"79","author":"Kunos","year":"2017","journal-title":"Cancer Chemother. 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