{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T23:07:16Z","timestamp":1769123236842,"version":"3.49.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"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":["LA\/P\/0056\/2020"],"award-info":[{"award-number":["LA\/P\/0056\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/QUI-QIN\/0586\/2020"],"award-info":[{"award-number":["PTDC\/QUI-QIN\/0586\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/135797\/2018"],"award-info":[{"award-number":["SFRH\/BD\/135797\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/100\/2025"],"award-info":[{"award-number":["UID\/100\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem. Biol."],"abstract":"<jats:p>\n                    Cancer treatment remains a public health challenge, requiring, more than ever, the development of effective and selective therapeutic drugs. Metal complexes of 8-hydroxyquinoline (8HQ) have long been recognized to exhibit significant potential in this field due to its potent chelating properties, stability, and broad spectrum of bioactivity. When coordinated to a metal center with potential therapeutic properties, synergistic or additive effects can be achieved. This mini-review summarizes the synthesis, characterization, and biological evaluation of metal complexes (Zn, Cu, V, Ni, Fe and Ru) of 8-hydroxyquinoline derived ligands, which were recently developed in our group. The focus was on 8HQ ligands substituted at position 2 by an imine, with particular attention given to the challenges of selectivity and solubility. Malignant melanoma, colon, lung and triple-negative breast cancers were selected for the\n                    <jats:italic>in vitro<\/jats:italic>\n                    screening of the complexes\u2019 anticancer properties. Cellular assays revealed that the mechanisms of action involve reactive oxygen species (ROS) generation and apoptotic cell death. A nanoliposomal encapsulation strategy was employed to deliver the drugs passively and overcome selectivity and aqueous solubility issues\n                    <jats:italic>in vivo<\/jats:italic>\n                    . The key findings demonstrate the potential of these complexes in both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    settings, supporting their application as next-generation anticancer therapies.\n                  <\/jats:p>","DOI":"10.3389\/fchbi.2026.1734289","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:53:06Z","timestamp":1769064786000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anticancer drugs based on metal complexes of 2-imine-8-hydroxyquinolines"],"prefix":"10.3389","volume":"5","author":[{"given":"Leonor","family":"C\u00f4rte-Real","sequence":"first","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural and Departamento de Engenharia Qu\u00edmica, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa","place":["Lisboa, Portugal"]}]},{"given":"N\u00e1dia","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural and Departamento de Engenharia Qu\u00edmica, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa","place":["Lisboa, Portugal"]}]},{"given":"Isabel","family":"Correia","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural and Departamento de Engenharia Qu\u00edmica, Institute of Molecular Sciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa","place":["Lisboa, Portugal"]}]}],"member":"1965","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"886","DOI":"10.3390\/antibiotics12050886","article-title":"Harnessing the dual antimicrobial mechanism of action with Fe(8-Hydroxyquinoline)(3) to develop a topical ointment for mupirocin-resistant MRSA infections","volume":"12","author":"Abeydeera","year":"2023","journal-title":"Antibiotics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.addr.2012.09.037","article-title":"Liposomal drug delivery systems: from concept to clinical applications","volume":"65","author":"Allen","year":"2013","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"828","DOI":"10.3390\/met11050828","article-title":"Vanadium and melanoma: a systematic review","volume":"11","author":"Amante","year":"2021","journal-title":"Metals"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1021\/mp400592n","article-title":"Oxidative stress induced by copper and iron complexes with 8-Hydroxyquinoline derivatives causes paraptotic death of HeLa cancer cells","volume":"11","author":"Barilli","year":"2014","journal-title":"Mol. Pharm."},{"key":"B5","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3390\/pharmaceutics9020012","article-title":"Liposomal formulations in clinical use: an updated review","volume":"9","author":"Bulbake","year":"2017","journal-title":"Pharmaceutics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1021\/ml300238z","article-title":"Synthesis of 8-Hydroxyquinoline derivatives as novel antitumor agents","volume":"4","author":"Chan","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"B7","doi-asserted-by":"publisher","first-page":"6596","DOI":"10.1039\/d0dt01017k","article-title":"In vitro antiproliferative effect of vanadium complexes bearing 8-hydroxyquinoline-based ligands \u2013 the substituent effect","volume":"49","author":"Choroba","year":"2020","journal-title":"Dalton Trans."},{"key":"B8","doi-asserted-by":"publisher","first-page":"125643","DOI":"10.1016\/j.ijpharm.2025.125643","article-title":"Liposomal nanoformulations of novel copper-based complexes exhibiting antimelanoma activity \u2013 in vitro and in vivo validation","volume":"677","author":"Coelho","year":"2025","journal-title":"Int. J. Pharm."},{"key":"B9","doi-asserted-by":"publisher","first-page":"11466","DOI":"10.1021\/acs.inorgchem.3c01066","article-title":"Cu(II) and Zn(II) complexes of new 8-Hydroxyquinoline schiff bases: investigating their structure, solution speciation, and anticancer potential","volume":"62","author":"C\u00f4rte-Real","year":"2023","journal-title":"Inorg. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"9416","DOI":"10.1039\/d4dt00733f","article-title":"Enhanced selectivity towards melanoma cells with zinc(ii)-schiff bases containing imidazole derivatives","volume":"53","author":"C\u00f4rte-Real","year":"2024","journal-title":"Dalton Trans."},{"key":"B11","doi-asserted-by":"publisher","first-page":"4822","DOI":"10.3390\/ijms24054822","article-title":"Zinc: from biological functions to therapeutic potential","volume":"24","author":"Costa","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.jconrel.2019.12.023","article-title":"The role of liposomes in clinical nanomedicine development. What now? Now what?","volume":"318","author":"Crommelin","year":"2020","journal-title":"J. Control Rel."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1002\/iub.253","article-title":"Metal ionophores - an emerging class of anticancer drugs","volume":"61","author":"Ding","year":"2009","journal-title":"IUBMB Life"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4737","DOI":"10.1039\/d3dt00150d","article-title":"Synthesis and anticancer mechanisms of zinc(ii)-8-hydroxyquinoline complexes with 1,10-phenanthroline ancillary ligands","volume":"52","author":"Du","year":"2023","journal-title":"Dalton Trans."},{"key":"B15","volume-title":"Global cancer observatory: cancer today","author":"Ferlay","year":"2024"},{"key":"B16","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.microc.2016.12.007","article-title":"Comparative in vitro investigation of anticancer copper chelating agents","volume":"136","author":"Ga\u00e1l","year":"2018","journal-title":"Microchem. J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/s0020-1693(02)01483-4","article-title":"Oxovanadium(IV) complexes of quinoline derivatives","volume":"348","author":"Garribba","year":"2003","journal-title":"Inorg. Chim. Acta."},{"key":"B18","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.addr.2018.07.007","article-title":"Tumor targeting via EPR: strategies to enhance patient responses","volume":"130","author":"Golombek","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2906","DOI":"10.1021\/acs.jpca.7b12632","article-title":"Elucidating the solution-phase structure and behavior of 8-Hydroxyquinoline zinc in DMSO","volume":"122","author":"Grice","year":"2018","journal-title":"J. Phys. Chem. A"},{"key":"B20","doi-asserted-by":"publisher","first-page":"104633","DOI":"10.1016\/j.bioorg.2021.104633","article-title":"Insights of 8-hydroxyquinolines: a novel target in medicinal chemistry","volume":"108","author":"Gupta","year":"2021","journal-title":"Bioorg. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.ccr.2015.03.010","article-title":"The chemistry and biology of vanadium compounds in cancer therapeutics","author":"Kioseoglou","year":"2015","journal-title":"Coord. Chem. .Rev."},{"key":"B22","doi-asserted-by":"publisher","first-page":"150","DOI":"10.3390\/inorganics13050150","article-title":"Novel 8-Hydroxyquinoline-Derived V(IV)O, Ni(II), and Fe(III) complexes: synthesis, characterization, and in vitro cytotoxicity against tumor cells","volume":"13","author":"Lopes","year":"2025","journal-title":"Inorganics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.ejmech.2016.05.007","article-title":"8-Hydroxyquinolines in medicinal chemistry: a structural perspective","volume":"120","author":"Oliveri","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"11045","DOI":"10.1039\/c8dt03088j","article-title":"Impact of copper and iron binding properties on the anticancer activity of 8-hydroxyquinoline derived mannich bases","volume":"47","author":"Pape","year":"2018","journal-title":"Dalton Trans."},{"key":"B25","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ccr.2014.12.002","article-title":"Vanadium compounds in medicine","volume":"301","author":"Pessoa","year":"2015","journal-title":"Coord. Chem. Rev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.2147\/DDDT.S49763","article-title":"8-Hydroxyquinolines: a review of their metal chelating properties and medicinal applications","volume":"7","author":"Prachayasittikul","year":"2013","journal-title":"Drug Des. devel. Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"6728","DOI":"10.3390\/ijms23126728","article-title":"Liposomal formulations of a new Zinc(II) complex exhibiting high therapeutic potential in a murine Colon cancer model","volume":"23","author":"Ribeiro","year":"","journal-title":"Int. J. Mol. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.3390\/pharmaceutics14122583","article-title":"Metal coordination and biological screening of a schiff base derived from 8-Hydroxyquinoline and benzothiazole","volume":"14","author":"Ribeiro","year":"","journal-title":"Pharmaceutics"},{"key":"B29","doi-asserted-by":"publisher","first-page":"111932","DOI":"10.1016\/j.jinorgbio.2022.111932","article-title":"Solution chemical properties and anticancer potential of 8-hydroxyquinoline hydrazones and their oxidovanadium(IV) complexes J, inorg","volume":"235","author":"Ribeiro","year":"","journal-title":"Biochem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1106349","DOI":"10.3389\/fchem.2023.1106349","article-title":"Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes","volume":"11","author":"Ribeiro","year":"2023","journal-title":"Front. Chem."},{"key":"B31","doi-asserted-by":"publisher","first-page":"111984","DOI":"10.1016\/j.jinorgbio.2022.111984","article-title":"Do bioactive 8-hydroxyquinolines oxidovanadium(IV) and (V) complexes inhibit the growth of M. Smegmatis?","volume":"237","author":"Scalese","year":"2022","journal-title":"J. Inorg. Biochem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jinorgbio.2017.12.002","article-title":"Simple and mixed complexes of copper(II) with 8-hydroxyquinoline derivatives and amino acids: characterization in solution and potential biological implications","volume":"180","author":"Sgarlata","year":"2018","journal-title":"J. Inorg. Biochem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1007\/s00775-018-1596-y","article-title":"Anti-prostate cancer activity of 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazide copper complexes in vivo by bioluminescence imaging","volume":"23","author":"Xie","year":"2018","journal-title":"J. Biol. Inorg. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.3390\/ijms19071874","article-title":"Crystal structures, and antitumor activities of Copper(II) and Nickel(II) complexes with 2-((2-(Pyridin-2-yl)hydrazono)methyl)quinolin-8-ol","volume":"19","author":"Yang","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/s00775-007-0299-6","article-title":"Synthesis and characterization of new copper thiosemicarbazone complexes with an ONNS quadridentate system: cell growth inhibition, S-phase cell cycle arrest and proapoptotic activities on cisplatin-resistant neuroblastoma cells","volume":"13","author":"Zhang","year":"2008","journal-title":"J. Biol. Inorg. Chem."}],"container-title":["Frontiers in Chemical Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchbi.2026.1734289\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:53:10Z","timestamp":1769064790000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchbi.2026.1734289\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":35,"alternative-id":["10.3389\/fchbi.2026.1734289"],"URL":"https:\/\/doi.org\/10.3389\/fchbi.2026.1734289","relation":{},"ISSN":["2813-530X"],"issn-type":[{"value":"2813-530X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]},"article-number":"1734289"}}