{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T17:49:42Z","timestamp":1785606582156,"version":"3.56.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent in vitro investigations of <jats:italic>N,N\u2032<\/jats:italic>\u2010bis(salicylidene)\u20101,2\u2010phenylenediamine (SAP) iron(III) complexes substituted with alkyl (ethyl, propyl, butyl) carboxylates at position 4 in tumor and leukemia cells revealed strong cytotoxic activity. In continuation of this study, analogous nickel(II) and cobalt(III) complexes were synthesized and tested in HL\u201060 leukemia, and cisplatin\u2010sensitive and \u2010resistant A2780 ovarian cancer cell lines. The biological activity depended on the extent of cellular uptake and the formation of reactive oxygen species (ROS). Inactive [(Ni(II)SAP] complexes (<jats:bold>1\u22123<\/jats:bold>) only marginally accumulated in tumor cells and did not induce ROS. The cellular uptake of [Co(III)SAP]Cl complexes (<jats:bold>4\u22126<\/jats:bold>) into the cells depended on the length of the ester alkyl chain (ethyl, <jats:bold>4<\/jats:bold> &lt; propyl, <jats:bold>5<\/jats:bold> &lt; butyl, <jats:bold>6<\/jats:bold>). The cytotoxicity correlated with the presence of ROS. The low cytotoxic complex <jats:bold>4<\/jats:bold> induced only few ROS, while <jats:bold>5<\/jats:bold> and <jats:bold>6<\/jats:bold> caused a good to outstanding antiproliferative activity, exerted high ROS generation, and induced cell death after 48\u2009h. Necrostatin\u20101 prevented the biological effects, proving necroptosis as part of the mode of action. Interestingly, the effects of <jats:bold>5<\/jats:bold> and <jats:bold>6<\/jats:bold> were not reversed by Ferrostatin\u20101, but even enhanced upon simultaneous application to the tumor cells.<\/jats:p>","DOI":"10.1002\/ardp.202200655","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T09:26:55Z","timestamp":1675416415000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Synthesis and biological evaluation of salophen nickel(II) and cobalt(III) complexes as potential anticancer compounds"],"prefix":"10.1002","volume":"356","author":[{"given":"Benjamin N.","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI\u2014Center for Molecular Biosciences Innsbruck, CCB\u2014Center for Chemistry and Biomedicine University of Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1963-9838","authenticated-orcid":false,"given":"Daniel","family":"Baecker","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI\u2014Center for Molecular Biosciences Innsbruck, CCB\u2014Center for Chemistry and Biomedicine University of Innsbruck Innsbruck Austria"},{"name":"Tyrolean Cancer Research Institute  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6666-465X","authenticated-orcid":false,"given":"Hubert","family":"Descher","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI\u2014Center for Molecular Biosciences Innsbruck, CCB\u2014Center for Chemistry and Biomedicine University of Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Brandstaetter","sequence":"additional","affiliation":[{"name":"Tyrolean Cancer Research Institute  Innsbruck Austria"},{"name":"Immunobiology and Stem Cell Laboratory, Department of Internal Medicine V (Hematology and Oncology) Medical University of Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2213-3448","authenticated-orcid":false,"given":"Martin","family":"Hermann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Medical University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1624-2664","authenticated-orcid":false,"given":"Brigitte","family":"Kircher","sequence":"additional","affiliation":[{"name":"Tyrolean Cancer Research Institute  Innsbruck Austria"},{"name":"Immunobiology and Stem Cell Laboratory, Department of Internal Medicine V (Hematology and Oncology) Medical University of Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0427-4012","authenticated-orcid":false,"given":"Ronald","family":"Gust","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Institute of Pharmacy, CMBI\u2014Center for Molecular Biosciences Innsbruck, CCB\u2014Center for Chemistry and Biomedicine University of Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.102925"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.691795"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CS00033E"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2020.213339"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0DT02135K"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5NJ00594A"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5DT02101D"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ica.2017.06.060"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-009-0485-9"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2010.08.037"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002303"},{"key":"e_1_2_7_13_1","first-page":"17","volume":"3","author":"Lange T. 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