{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:03:32Z","timestamp":1790899412912,"version":"4.1.0"},"reference-count":91,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002923","name":"CONICET","doi-asserted-by":"publisher","award":["PIP 2051"],"award-info":[{"award-number":["PIP 2051"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"ANPCyT","doi-asserted-by":"publisher","award":["PICT 2019\u20102322"],"award-info":[{"award-number":["PICT 2019\u20102322"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["2SC1GM127278\u201007A1"],"award-info":[{"award-number":["2SC1GM127278\u201007A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,2,25]]},"abstract":"<jats:p>\n                    Triple\u2010negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic treatments. This study evaluates the anticancer activity and mode of action of the copper(II) complex [Cu(HL\n                    <jats:sup>1<\/jats:sup>\n                    )(NO\n                    <jats:sub>3<\/jats:sub>\n                    )H\n                    <jats:sub>2<\/jats:sub>\n                    O]\u00b7H\n                    <jats:sub>2<\/jats:sub>\n                    O (\n                    <jats:bold>CuHL<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>1<\/jats:bold>\n                    <\/jats:sup>\n                    ), derived from (E)\u2010N\u2019\u2010(2\u2010hydroxy\u20103\u2010methoxybenzylidene)furan\u20102\u2010carbohydrazide (\n                    <jats:bold>H<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>2<\/jats:bold>\n                    <\/jats:sub>\n                    <jats:bold>L<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>1<\/jats:bold>\n                    <\/jats:sup>\n                    ), against a panel of TNBC cell lines (MDA\u2010MB\u2010231, MDA\u2010MB\u2010468, MDA\u2010MB\u2010157, HCC1806).\n                    <jats:bold>CuHL<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>1<\/jats:bold>\n                    <\/jats:sup>\n                    exhibits potent cytotoxicity in the low micromolar range (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009\u2248\u20092\u2009\u00b5M), surpassing cisplatin by up to 81\u2010fold. In MDA\u2010MB\u2010231 cells,\n                    <jats:bold>CuHL<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>1<\/jats:bold>\n                    <\/jats:sup>\n                    inhibits colony formation and induced reactive oxygen species (ROS) generation in a concentration\u2010dependent manner. Moreover,\n                    <jats:bold>CuHL<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>1<\/jats:bold>\n                    <\/jats:sup>\n                    triggers apoptosis as evidenced by Annexin V\/PI staining and the modulation of Bax, Bcl\u20102, caspase\u20103, and cleaved caspase\u20103 protein levels. Label\u2010free quantitative proteomics reveal 34 differentially expressed proteins, implicating pathways related to heat shock response, protein folding, lipid metabolism, and cell migration. Notably,\n                    <jats:bold>CuHL<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>1<\/jats:bold>\n                    <\/jats:sup>\n                    downregulates BCAR3, AJUBA, MPZL1, TP53, FASN, and HMGCS1, suggesting inhibition of prometastatic and lipid biosynthetic processes. Functional assays confirm reduced migratory capacity in MDA\u2010MB\u2010231 cells. These findings position\n                    <jats:bold>CuHL<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>1<\/jats:bold>\n                    <\/jats:sup>\n                    as a promising candidate for TNBC therapy, meriting further in\u2009vivo evaluation.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500836","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:34:21Z","timestamp":1771418061000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the Anticancer Properties and Mode of Action of Copper(II)\u2010Furan Acylhydrazone on Human Triple Negative Breast Cancer Cells"],"prefix":"10.1002","volume":"21","author":[{"given":"Luc\u00eda","family":"Santa Maria de la Parra","sequence":"first","affiliation":[{"name":"Centro de Qu\u00edmica Inorg\u00e1nica (CEQUINOR, UNLP, CCT\u2010CONICET La Plata, Asociado a CIC) Departamento de Qu\u00edmica Facultad de Ciencias Exactas Universidad Nacional de La Plata  Bv 120 1465 La Plata B1900 Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria R.","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Cardiovasculares \u2018Dr. Horacio E. Cingolani\u2019 Facultad de Ciencias M\u00e9dicas de La Plata Universidad Nacional de La Plata  Avenue. 60 y 120 La Plata B1900 Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazia","family":"Nayeem","sequence":"additional","affiliation":[{"name":"Brooklyn College Cancer Center BCCC\u2010CURE Brooklyn College Department The City University of New York  2900 Bedford Avenue Brooklyn New York 11210 USA"},{"name":"Biology PhD Programs The Graduate Center The City University of New York  365 Fifth Avenue New York NY 10016 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Contel","sequence":"additional","affiliation":[{"name":"Brooklyn College Cancer Center BCCC\u2010CURE Brooklyn College Department The City University of New York  2900 Bedford Avenue Brooklyn New York 11210 USA"},{"name":"Biology PhD Programs The Graduate Center The City University of New York  365 Fifth Avenue New York NY 10016 USA"},{"name":"Chemistry and Biochemistry Department Brooklyn College The City University of New York  2900 Bedford Avenue Brooklyn New York 11210 USA"},{"name":"Biochemistry PhD Programs The Graduate Center The City University of New York  365 Fifth Avenue New York NY 10016 USA"},{"name":"Chemistry PhD Programs The Graduate Center The City University of New York  365 Fifth Avenue New York NY 10016 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-3997","authenticated-orcid":false,"given":"Ignacio E.","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Inorg\u00e1nica (CEQUINOR, UNLP, CCT\u2010CONICET La Plata, Asociado a CIC) Departamento de Qu\u00edmica Facultad de Ciencias Exactas Universidad Nacional de La Plata  Bv 120 1465 La Plata B1900 Buenos Aires Argentina"},{"name":"Brooklyn College Cancer Center BCCC\u2010CURE Brooklyn College Department The City University of New York  2900 Bedford Avenue Brooklyn New York 11210 USA"},{"name":"Biology PhD Programs The Graduate Center The City University of New York  365 Fifth Avenue New York NY 10016 USA"},{"name":"C\u00e1tedra de Fisiopatolog\u00eda Departamento de Ciencias Biol\u00f3gicas Facultad de Ciencias Exactas Universidad Nacional de La Plata  La Plata B1900 Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03502-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2022.02.003"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-022-00468-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00565-2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01341-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01805-y"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202100438"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.101893"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2023.215507"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2126"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27559-z"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.4c02188"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41063-x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-024-05641-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-006-0364-9"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201710910"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2019.110975"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7DT00283A"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087531"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2018.07.015"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1515\/biol-2022-0840"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.9b00284"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867328666211117094550"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.3c04085"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1DT00869B"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202100520"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2023.110685"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/inorganics9020009"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.poly.2021.115621"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ica.2018.11.039"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4DT03445G"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9NJ04975D"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8NJ06274A"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202100325"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.13381"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202000122"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10534-015-9831-2"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25112530"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.339"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2005.12.009"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28176401"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12521"},{"key":"e_1_2_10_44_1","doi-asserted-by":"crossref","unstructured":"E.Eruslanov S.Kusmartsev 2010 57\u201372.","DOI":"10.1007\/978-1-60761-411-1_4"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11137"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(19980101)31:1<1::AID-CYTO1>3.0.CO;2-R"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1000"},{"key":"e_1_2_10_48_1","doi-asserted-by":"crossref","unstructured":"M.Zhang X.Bi 2024 Multidisciplinary Digital Publishing Institute (MDPI) preprint DOI: 10.3390\/ijms25020876.","DOI":"10.3390\/ijms25020876"},{"key":"e_1_2_10_49_1","unstructured":"E.Tiligada 2006. inEndocr Relat Cancer ."},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00266.2016"},{"key":"e_1_2_10_51_1","doi-asserted-by":"crossref","unstructured":"P.Walter D.Ron 2011 https:\/\/doi.org\/10.1126\/science.1209038.","DOI":"10.1126\/science.1209038"},{"key":"e_1_2_10_52_1","doi-asserted-by":"crossref","unstructured":"M.Wang R. J.Kaufman 2016 https:\/\/doi.org\/10.1038\/nature17041.","DOI":"10.1038\/nature17041"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910293"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1137\/040608635"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13185"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1992.tb16961.x"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2002611"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.366"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-19-0243"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205391200"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20020935"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0320831"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/3321409"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1306"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065678"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3455"},{"key":"e_1_2_10_67_1","unstructured":"J.Arras K. S.Thomas P. J.Myers A. M.Cross A. D.Osei G. E.Vazquez K. A.Atkins M. R.Conaway M. K.Jones M. J.Lazzara A. H.Bouton Breast Cancer Antiestrogen Resistance 3 (BCAR3) Promotes Tumor Growth and Progression in Triple\u2010Negative Breast Cancer 2021."},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.89"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.27"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.04.013"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/35042675"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.11.026"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgs232"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209735"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13258-013-0154-9"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt703"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.10.001"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.11.025"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-021-00238-y"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3MD00145H"},{"key":"e_1_2_10_81_1","doi-asserted-by":"crossref","unstructured":"L.Grogan P.Shapiro 2024 181\u2013207.","DOI":"10.1016\/bs.apha.2024.04.001"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2024.2400167"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.06.190"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/369321a0"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90509-O"},{"key":"e_1_2_10_86_1","unstructured":"A. G.Porter R. U.Ja \u00c8.Nicke Emerging Roles of Caspase\u20103 in Apoptosis n.d."},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11101971"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2023.104619"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2023.112326"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1QI00233C"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45014"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7493-1_7"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500836","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202500836","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500836","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:12:16Z","timestamp":1773004336000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202500836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":91,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,2,25]]}},"alternative-id":["10.1002\/cmdc.202500836"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202500836","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"assertion":[{"value":"2025-09-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500836"}}