{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T22:41:28Z","timestamp":1778539288169,"version":"3.51.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/00100\/2020 UIDP\/00100\/2020 La\/P\/0056\/2000 PTDC\/QUI-QIN\/0586\/2020 SFRH\/BD\/135797\/2018 UIDB\/04046\/2020 UIDP\/04046\/2020 NECL\u2014proj. 22096"],"award-info":[{"award-number":["UIDB\/00100\/2020 UIDP\/00100\/2020 La\/P\/0056\/2000 PTDC\/QUI-QIN\/0586\/2020 SFRH\/BD\/135797\/2018 UIDB\/04046\/2020 UIDP\/04046\/2020 NECL\u2014proj. 22096"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014810","name":"Fondazione di Sardegna","doi-asserted-by":"publisher","award":["FdSGarribba2017"],"award-info":[{"award-number":["FdSGarribba2017"]}],"id":[{"id":"10.13039\/100014810","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:p>We report the synthesis and characterization of a group of benzoylhydrazones (L<jats:sup>n<\/jats:sup>) derived from 2-carbaldehyde-8-hydroxyquinoline and benzylhydrazides containing distinct <jats:italic>para<\/jats:italic> substituents (R = H, Cl, F, CH<jats:sub>3<\/jats:sub>, OCH<jats:sub>3<\/jats:sub>, OH and NH<jats:sub>2<\/jats:sub>, for L<jats:sup>1-7<\/jats:sup>, respectively; in L<jats:sup>8<\/jats:sup> isonicotinohydrazide was used instead of benzylhydrazide). Cu(II) complexes were prepared by reaction of each benzoylhydrazone with Cu(II) acetate. All compounds were characterized by elemental analysis and mass spectrometry as well as by FTIR, UV-visible absorption, NMR or electron paramagnetic resonance spectroscopies. Complexes isolated in the solid state (<jats:bold>1\u20138<\/jats:bold>) are either formulated as [Cu(HL)acetate] (with L<jats:sup>1<\/jats:sup> and L<jats:sup>4<\/jats:sup>) or as [Cu(L<jats:sup>n<\/jats:sup>)]<jats:sub>3<\/jats:sub> (<jats:italic>n<\/jats:italic> = 2, 3, 5, 6, 7 and 8). Single crystal X-ray diffraction studies were done for L<jats:sup>5<\/jats:sup> and [Cu(L<jats:sup>5<\/jats:sup>)]<jats:sub>3<\/jats:sub>, confirming the trinuclear formulation of several complexes. Proton dissociation constants, lipophilicity and solubility were determined for all free ligands by UV-Vis spectrophotometry in 30% (v\/v) DMSO\/H<jats:sub>2<\/jats:sub>O. Formation constants were determined for [Cu(LH)], [Cu(L)] and [Cu(LH<jats:sub>\u22121<\/jats:sub>)] for L = L<jats:sup>1<\/jats:sup>, L<jats:sup>5<\/jats:sup> and L<jats:sup>6<\/jats:sup>, and also [Cu(LH<jats:sub>\u22122<\/jats:sub>)] for L = L<jats:sup>6<\/jats:sup>, and binding modes are proposed, [Cu(L)] predominating at physiological pH. The redox properties of complexes formed with L<jats:sup>1<\/jats:sup>, L<jats:sup>5<\/jats:sup> and L<jats:sup>6<\/jats:sup> are investigated by cyclic voltammetry; the formal redox potentials fall in the range of +377 to +395\u00a0mV vs. NHE. The binding of the Cu(II)-complexes to bovine serum albumin was evaluated by fluorescence spectroscopy, showing moderate-to-strong interaction and suggesting formation of a ground state complex. The interaction of L<jats:sup>1<\/jats:sup>, L<jats:sup>3<\/jats:sup>, L<jats:sup>5<\/jats:sup> and L<jats:sup>7<\/jats:sup>, and of the corresponding complexes with <jats:italic>calf thymus<\/jats:italic> DNA was evaluated by thermal denaturation. The antiproliferative activity of all compounds was evaluated in malignant melanoma (A-375) and lung (A-549) cancer cells. The complexes show higher activity than the corresponding free ligand, and most complexes are more active than cisplatin. Compounds <jats:bold>1, 3, 5<\/jats:bold>, and <jats:bold>8<\/jats:bold> were selected for additional studies: while these complexes induce reactive oxygen species and double-strand breaks in both cancer cells, their ability to induce cell-death by apoptosis varies. Within the set of compounds tested, <jats:bold>8<\/jats:bold> emerges as the most promising one, presenting low IC<jats:sub>50<\/jats:sub> values, and high induction of oxidative stress and DNA damage, which eventually lead to high rates of apoptosis.<\/jats:p>","DOI":"10.3389\/fchem.2023.1106349","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T06:02:21Z","timestamp":1679378541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes"],"prefix":"10.3389","volume":"11","author":[{"given":"N\u00e1dia","family":"Ribeiro","sequence":"first","affiliation":[]},{"given":"Ipek","family":"Bulut","sequence":"additional","affiliation":[]},{"given":"Baris","family":"Sergi","sequence":"additional","affiliation":[]},{"given":"Vivien","family":"P\u00f3sa","sequence":"additional","affiliation":[]},{"given":"Gabriella","family":"Spengler","sequence":"additional","affiliation":[]},{"given":"Giuseppe","family":"Sciortino","sequence":"additional","affiliation":[]},{"given":"V\u00e2nia","family":"Andr\u00e9","sequence":"additional","affiliation":[]},{"given":"Liliana P.","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Tarita","family":"Biver","sequence":"additional","affiliation":[]},{"given":"Valeria","family":"Ugone","sequence":"additional","affiliation":[]},{"given":"Eugenio","family":"Garribba","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Costa-Pessoa","sequence":"additional","affiliation":[]},{"given":"\u00c9va A.","family":"Enyedy","sequence":"additional","affiliation":[]},{"given":"Ceyda","family":"Acilan","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Correia","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3757","DOI":"10.1039\/B507621H","article-title":"2-[(8-Hydroxyquinolinyl)Methylene]Hydrazinecarboxamide: Expanding the coordination sphere of 8-hydroxyquinoline for coordination of rare-earth metal(III) ions","author":"Albrecht","year":"2005","journal-title":"Dalton Trans."},{"key":"B2","doi-asserted-by":"publisher","first-page":"14362","DOI":"10.1039\/d1ra00172h","article-title":"Ligand substituent effect on the cytotoxicity activity of two new copper(II) complexes bearing 8-hydroxyquinoline derivatives: Validated by MTT assay and apoptosis in MCF-7 cancer cell line (human breast cancer)","volume":"11","author":"Ali","year":"2021","journal-title":"RCS Adv."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3937","DOI":"10.1016\/j.ica.2005.06.063","article-title":"Synthetic, EPR spectroscopic, magnetic and X-ray crystallographic structural studies on copper(II) complexes of the tridentate N2S donor ligand formed from 6-methyl-2-formylpyridine and S-methyldithiocarbazate (hmpsme)","volume":"358","author":"Ali","year":"2005","journal-title":"Inorg. 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