{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T02:59:30Z","timestamp":1785380370444,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["ChemistryOpen"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    The demand for novel, selective anticancer agents, driven by drug resistance and systemic toxicity of current treatments, underscores the importance of targeted drug discovery. Present research involved cytotoxic screening of a series of synthesized copper nanocatalyzed carbonyl\u2010functionalized triazoles (\n                    <jats:bold>3a<\/jats:bold>\n                    <jats:bold>\u2013<\/jats:bold>\n                    <jats:bold>p<\/jats:bold>\n                    ), where\n                    <jats:bold>3i<\/jats:bold>\n                    and\n                    <jats:bold>3j<\/jats:bold>\n                    have shown highest selectivity index (SI) scores of 2.30 and 4.44, respectively. Computational validation of the lead compounds demonstrated specific interaction with BCL2\u2010associated X protein (BAX) and BCL2, characterized by strong binding affinities ranging between \u22126.73 and \u22127.70\u2009kcal\/mol. Corresponding protein\u2013ligand complexes demonstrated robust conformational stability throughout their 100\u2009ns of molecular dynamics simulation. Subsequent in\u2009vitro validation using MCF\u20107 cells firmly corroborated the in\u2009silico findings, by revealing significant upregulation of BAX (\n                    <jats:italic>p\u2009<\/jats:italic>\n                    &lt;\u20090.001) and downregulation of BCL2 (\n                    <jats:italic>p\u2009<\/jats:italic>\n                    &lt;\u20090.001). Compound induced cellular stress, elevated the ROS\u2010producing cell population up to 40%. Resulting cellular oxidative stress, rapidly depleted the glutathione reserves up to 50% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), consequently compromising the mitochondrial membrane potential leading to mitochondrial dysfunction. Furthermore, the compound induced S\u2010phase cell cycle arrest (upto 51.5%), played a pivotal role in promoting apoptosis by activating DNA damage response pathways. In conclusion, this study has successfully identified two lead compounds (\n                    <jats:bold>3i<\/jats:bold>\n                    &amp;\n                    <jats:bold>3j<\/jats:bold>\n                    ) that modulate multiple converging oncogenic pathways, providing compelling preclinical candidates for targeted management of breast cancer.\n                  <\/jats:p>","DOI":"10.1002\/open.202500543","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T14:11:11Z","timestamp":1768572671000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated In\u2009Silico and In\u2009Vitro Study of Copper Nanocatalyzed Carbonyl\u2010Functionalized Triazoles\u2014Inducing S Phase Cell Cycle Arrest and Apoptosis in MCF\u20107"],"prefix":"10.1002","volume":"15","author":[{"given":"Joydip","family":"Mondal","sequence":"first","affiliation":[{"name":"School of Advanced Sciences Department of Chemistry Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiasha","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology Department of Bio\u2010Medical Sciences Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitluri Kiran","family":"Kumar","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology Department of Bio\u2010Medical Sciences Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasanth Babu","family":"Nandagopal","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology Department of Bio\u2010Medical Sciences Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadananda","family":"Mal","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology Department of Bio\u2010Medical Sciences Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourav","family":"Paul","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology Department of Bio\u2010Medical Sciences Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"S","sequence":"additional","affiliation":[{"name":"School of Advanced Sciences Department of Chemistry Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chayan","family":"Pandya","sequence":"additional","affiliation":[{"name":"School of Advanced Sciences Department of Chemistry Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac Arnold","family":"Emerson","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology Department of Bio\u2010Medical Sciences Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5668-100X","authenticated-orcid":false,"given":"Venkatraman","family":"Manickam","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology Department of Bio\u2010Medical Sciences Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5208-6307","authenticated-orcid":false,"given":"Akella","family":"Sivaramakrishna","sequence":"additional","affiliation":[{"name":"School of Advanced Sciences Department of Chemistry Vellore Institute of Technology (VIT)  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3RA00056G"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010020\u201000630\u20103"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2015.03.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/S40779\u2010025\u201000595\u20102"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41392\u2010022\u201001110\u2010Y"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41419\u2010019\u20101407\u20106"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16132478"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2025.13537"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010020\u20100341\u2010y"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.864286"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.8b00582"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2660475"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26213"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.134487"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2013.01.081"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202304871"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo5004339"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1cc06477k"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/2892081"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.4103\/apjtb.apjtb_823_23"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.1c02193"},{"key":"e_1_2_10_23_1","unstructured":"EEruslanov Advanced Protocols in Oxidative Stress II \u2013 Google Scholar accessed September 16 2025 https:\/\/scholar.google.com\/scholar_lookup?title=Advanced%20Protocols%20in%20Oxidative%20Stress%20II&author=E.%20Eruslanov%20&author=S.%20Kusmartsev%20&publication_year=2010&."},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005\u20102728(03)00110\u20105"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSMBR.893327"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.15171\/bi.2015.01"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15068"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10050642"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010020\u20100384\u20102"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5381692"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20874"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.04.043"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4002"},{"key":"e_1_2_10_34_1","first-page":"1","article-title":"Detection of Total Reactive Oxygen Species in Adherent Cells by 2\u2032,7\u2032\u2010Dichlorodihydrofluorescein Diacetate Staining","volume":"2020","author":"Kim H.","year":"2020","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2005.12.009"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.98106s51229"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/972913"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121110"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10101429"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3803"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u201061779\u2010382\u20100_12"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.06.001"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-022-00859-2"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2018.05.019"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114398"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.115081"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc6779"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010024\u201006939\u20105"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0928\u20104680(00)00053\u20105"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010023\u201000629\u20104"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0651-y"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349\u20107006.2004.tb03323.x"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-009-1001-1"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot4493"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0000000000000105"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0198\u20108859(01)00214\u20102"}],"container-title":["ChemistryOpen"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/open.202500543","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/open.202500543","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/open.202500543","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:36:27Z","timestamp":1772984187000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/open.202500543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/open.202500543"],"URL":"https:\/\/doi.org\/10.1002\/open.202500543","archive":["Portico"],"relation":{},"ISSN":["2191-1363","2191-1363"],"issn-type":[{"value":"2191-1363","type":"print"},{"value":"2191-1363","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500543"}}