{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:01:39Z","timestamp":1785142899289,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Febuxostat, a selective xanthine oxidase inhibitor, was modified via 1,2,3\u2010triazole\u2010based molecular hybridization to generate a series of derivatives with potential anticancer activity. Among them, compounds\n                    <jats:bold>8c<\/jats:bold>\n                    and\n                    <jats:bold>8e<\/jats:bold>\n                    exhibited significant antitumor effects across multiple cancer cell lines, particularly in HepG2 cells, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 6.96\u2009\u00b1\u20091.76 and 8.56\u2009\u00b1\u20091.93\u2009\u03bcM, respectively. Colony formation assays confirmed that both compounds markedly inhibited tumor cell proliferation. Annexin V\u2010FITC\/PI and TUNEL assays further demonstrated that\n                    <jats:bold>8c<\/jats:bold>\n                    and\n                    <jats:bold>8e<\/jats:bold>\n                    induced DNA damage and apoptosis in HepG2 cells, as shown by increased \u03b3\u2010H2AX expression and enhanced DNA strand breaks. They also activated intrinsic apoptotic pathways, including the cleavage and activation of caspase\u20109, caspase\u20103, and PARP. In vivo, nude mouse xenograft experiments validated their antitumor efficacy, with elevated cleaved caspase\u20103 levels in tumor tissues. Collectively, these findings indicate that\n                    <jats:bold>8c<\/jats:bold>\n                    and\n                    <jats:bold>8e<\/jats:bold>\n                    possess strong therapeutic potential against liver cancer and exhibit promising efficacy and safety profiles.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70263","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:51:44Z","timestamp":1780663904000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Anticancer Evaluation of Febuxostat\u2010Based Triazolyl Derivatives"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5260-1312","authenticated-orcid":false,"given":"Yao","family":"Lu","sequence":"first","affiliation":[{"name":"College of Basic Medicine and Forensic Medicine Henan University of Science and Technology  Luoyang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine and Forensic Medicine Henan University of Science and Technology  Luoyang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Basic Medicine and Forensic Medicine Henan University of Science and Technology  Luoyang Henan China"},{"name":"Department of Pharmacy, the First Affiliated Hospital and College of Clinical Medicine Henan University of Science and Technology  Luoyang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoyu","family":"He","sequence":"additional","affiliation":[{"name":"Centre for Artificial Intelligence\u2010Driven Drug Discovery, Faculty of Applied Sciences Macao Polytechnic University  Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Guo","sequence":"additional","affiliation":[{"name":"Centre for Artificial Intelligence\u2010Driven Drug Discovery, Faculty of Applied Sciences Macao Polytechnic University  Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixi","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, the First Affiliated Hospital and College of Clinical Medicine Henan University of Science and Technology  Luoyang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3043-6676","authenticated-orcid":false,"given":"Ling","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Basic Medicine and Forensic Medicine Henan University of Science and Technology  Luoyang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00240-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2015.08.014"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.11.048"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701320337"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031328"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19040970"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apcsb.2021.01.003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.05.002"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202100554"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2020.127304"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00636"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1997.tb00457.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12100956"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/org3040026"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1265289"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2026.109777"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-30-87"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-024-02306-9"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2012.00128"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0644-5_1"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7270.2005.00108.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041020"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-889-7:043"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt828"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-013-9644-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0306430"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.23106"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.70263","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.70263","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.70263","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:09:53Z","timestamp":1785139793000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.70263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/ardp.70263"],"URL":"https:\/\/doi.org\/10.1002\/ardp.70263","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2025-12-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70263"}}