{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:52:19Z","timestamp":1791366739670,"version":"4.3.1"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Quaternary benzo[c]phenanthridine alkaloids (QBAs), an important class of natural isoquinoline alkaloids, possess potential multiple anti\u2010cancer activities. By structural simulation, 29 2\u2010phenylphthalazin\u20102\u2010iums with anti\u2010cancer effects were designed and synthesized in our previous study. Breast cancer is one of the most frequent malignant tumors, which is closely related to the high mortality rate in women. The role and underlying mechanism of 2\u2010phenylphthalazin\u20102\u2010iums in repressing the growth and metastasis of human breast cancer were explored. The role of 2\u2010phenylphthalazin\u20102\u2010iums in regulating the proliferation and invasion of MCF\u20107 cells was evaluated in vitro and in a xenograft model. After treatment with 3\u2032,5\u2032\u2010diCl isomer (\n                    <jats:bold>29<\/jats:bold>\n                    ), the reactive oxygen species (ROS) levels, Fe\n                    <jats:sup>2+<\/jats:sup>\n                    concentration and glutathione (GSH) contents were assessed to evaluate the effect of the 2\u2010arylphthalazine salts on facilitating ferroptosis in MCF\u20107 cells. Compound\n                    <jats:bold>29<\/jats:bold>\n                    exhibited a dose\u2010 and time\u2010dependent cytotoxicity on MCF\u20107 cells. Compound\n                    <jats:bold>29<\/jats:bold>\n                    treatment effectively repressed the growth and metastasis of breast cancer in a xenograft model. We verified for the first time that compound\n                    <jats:bold>29<\/jats:bold>\n                    triggered ferroptosis of MCF\u20107 cells, as evidenced by increased Fe\n                    <jats:sup>2+<\/jats:sup>\n                    concentration, ROS level, and decreased GSH content. Mechanistically, compound\n                    <jats:bold>29<\/jats:bold>\n                    induced oxidative damage and ferroptosis via regulating p53\/SALC7A11 axis. Iron chelator deferoxamine restored the proliferation and invasion of MCF\u20107 cells treated with compound\n                    <jats:bold>29<\/jats:bold>\n                    through inhibiting ferroptosis. Significantly, compound\n                    <jats:bold>29<\/jats:bold>\n                    inhibited the growth of human breast cancer cells MCF\u20107\u2010derived tumor xenograft (CDX) models. Thus, 2\u2010phenylphthalazin\u20102\u2010iums represent promising leads for the development of novel anti\u2010breast cancer agents in the future.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70256","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:16:50Z","timestamp":1779185810000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Ferroptosis as a Novel Mechanism for Antitumor Activity of 2\u2010phenylphthalazin\u20102\u2010iums in Breast Cancer"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3448-3392","authenticated-orcid":false,"given":"Fang\u2010Jun","family":"Cao","sequence":"first","affiliation":[{"name":"Shaanxi Key Laboratory of Qinling Ecological Security Shaanxi Institute of Zoology Xi'an Shaanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, Xi'an Key Laboratory of Special Medicine and Health Engineering, Research Center for Special Medicine and Health Systems Engineering, NPU\u2010UAB Joint Laboratory for Bone Metabolism, School of Life Sciences Northwestern Polytechnical University Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tie\u2010Zhi","family":"Jin","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Qinling Ecological Security Shaanxi Institute of Zoology Xi'an Shaanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai\u2010Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Qinling Ecological Security Shaanxi Institute of Zoology Xi'an Shaanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Feng","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Qinling Ecological Security Shaanxi Institute of Zoology Xi'an Shaanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_2_9_2_1","article-title":"A Drug Repurposing Approach of Atorvastatin Calcium for Its Antiproliferative activity for Effective Treatment of Breast Cancer: In Vitro and In Vivo Assessment","volume":"7","author":"Dina M. G.","year":"2024","journal-title":"International Journal of Pharmaceutics"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vesic.2024.100039"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116615"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2024.105669"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202202983"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.14715\/cmb\/2024.70.3.26"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-38222-x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20140-7"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2018.10.007"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11101-013-9290-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.21873\/cgp.20385"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202200284"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.0c06507"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19999-3"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/0118761429269383231119062233"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.11.046"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16202"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112358"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116406"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.05.019"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfutfo.2023.11.002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10081795"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01621-y"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.03.006"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-08158-z"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13621"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612828666220217124542"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.05.006"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1819728116"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-7-13"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0948-3"},{"key":"e_1_2_9_33_1","first-page":"1","article-title":"Photoredox Catalysed Reductive Aminomethylation of Quaternary Benzophenanthridine Alkaloids","volume":"37","author":"Wang X. H.","year":"2022","journal-title":"Natural Product Research"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232415768"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202501042"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.70256","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.70256","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.70256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:09:59Z","timestamp":1791364199000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.70256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/ardp.70256"],"URL":"https:\/\/doi.org\/10.1002\/ardp.70256","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70256"}}