{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:28:21Z","timestamp":1787772501136,"version":"build-2784847793"},"reference-count":35,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,8,27]]},"abstract":"<jats:p>\n                    A new family of proline\u2010derived\n                    <jats:italic>N<\/jats:italic>\n                    \u2010heterocyclic carbene (NHC) gold(I) complexes was synthesized and fully characterized by multinuclear NMR spectroscopy and HRMS analysis. The incorporation of a proline\u2010based fragment into the NHC scaffold enabled the generation of both neutral and cationic Au(I) complexes with distinct electronic and steric properties. Stability studies demonstrated that the complexes remain stable under physiological\u2010like conditions for at least 48\u2009h. Biological evaluation against A549 lung adenocarcinoma and MDA\u2010MB\u2010231 triple\u2010negative breast cancer cells revealed that the cationic complexes\n                    <jats:bold>3<\/jats:bold>\n                    and\n                    <jats:bold>4<\/jats:bold>\n                    display remarkable cytotoxic activity, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values in the low micromolar range, outperforming cisplatin and, in some cases, auranofin. Mechanistic investigations showed that complex\n                    <jats:bold>4<\/jats:bold>\n                    induces apoptotic cell death associated with intracellular reactive oxygen species (ROS) generation and depolarization of the mitochondrial membrane potential, indicating a mitochondria\u2010mediated pathway. In addition, DNA\u2010binding studies demonstrated that all complexes interact with calf thymus DNA predominantly through an intercalative mode, with complexes\n                    <jats:bold>2<\/jats:bold>\n                    ,\n                    <jats:bold>3<\/jats:bold>\n                    , and\n                    <jats:bold>4<\/jats:bold>\n                    exhibiting the highest binding affinities. In addition, thioredoxin reductase inhibition assays revealed significant enzyme inhibition for the cationic complex\n                    <jats:bold>4<\/jats:bold>\n                    , supporting disruption of cellular redox homeostasis. Overall, these results identify proline\u2010functionalized Au(I)\u2013NHC complexes as promising multifunctional anticancer agents.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70432","type":"journal-article","created":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T01:35:06Z","timestamp":1786844106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proline\u2010Derived\n                    <i>N<\/i>\n                    \u2010Heterocyclic Carbene Gold(I) Complexes With Dual DNA Binding and Thioredoxin Reductase\u00a0Inhibition"],"prefix":"10.1002","volume":"21","author":[{"given":"Giacomo","family":"Cassar\u00e0","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Inorg\u00e1nica Instituto de S\u00edntesis Qu\u00edmica y Cat\u00e1lisis Homog\u00e9nea (ISQCH) CSIC\u2010Universidad de Zaragoza  Zaragoza Spain"},{"name":"Dipartimento di Scienze Chimiche Universit\u00e0 degli Studi di Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1943-0209","authenticated-orcid":false,"given":"Mar\u00eda","family":"Gil\u2010Moles","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Inorg\u00e1nica Instituto de S\u00edntesis Qu\u00edmica y Cat\u00e1lisis Homog\u00e9nea (ISQCH) CSIC\u2010Universidad de Zaragoza  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7345-9670","authenticated-orcid":false,"given":"Thomas","family":"Scattolin","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Chimiche Universit\u00e0 degli Studi di Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-0695","authenticated-orcid":false,"given":"M. Concepci\u00f3n","family":"Gimeno","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Inorg\u00e1nica Instituto de S\u00edntesis Qu\u00edmica y Cat\u00e1lisis Homog\u00e9nea (ISQCH) CSIC\u2010Universidad de Zaragoza  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1001389"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-022-00468-0"},{"key":"e_1_2_9_4_1","first-page":"115747","article-title":"Triple\u2010Negative Breast Cancer: Epidemiology, Molecular Features, Pathogenesis and Treatment Options","volume":"214","author":"Karim A. M.","year":"2023","journal-title":"Biochemical Pharmacology"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.02.019"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.04.006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00933H"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.2c00649"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202218000"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c02252"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.117137"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8CS00570B"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5CS00924C"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c00608"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4DT01663G"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1515\/pac-2018-0901"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4DT02299H"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201501458"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6DT02000C"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201800098"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6DT04862E"},{"key":"e_1_2_9_22_1","first-page":"1986","article-title":"Bioconjugation of Cyclometalated Gold(III) Lipoic Acid Fragments to Linear and Cyclic Breast Cancer Targeting Peptides","volume":"17","author":"\u015ami\u0142owicz D.","year":"2020","journal-title":"Molecular Pharmaceutics"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejic.201402103"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15267"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.8b00215"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00776"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/b906140a"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6DT04834J"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2005.08.031"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/B701677H"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2013.03.013"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00394a013"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.5c00579"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4MD00964A"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ceur.202500483"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(95)52023-6"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70432","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.70432","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:51:15Z","timestamp":1787770275000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.70432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,15]]},"references-count":35,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,8,27]]}},"alternative-id":["10.1002\/cmdc.70432"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.70432","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,15]]},"assertion":[{"value":"2026-05-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70432"}}