{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T09:01:24Z","timestamp":1794128484685,"version":"4.8.0"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Imidazole derivatives have a multi\u2010targeted ability that indicates their ability to act as anticancer agents in respect to breast cancer. This study aimed to evaluate the anticancer response of a new series of 1, 3, 5\u2010trisubstituted\u20102\u2010thioxo\u2010imidazoles derivatives (\n                    <jats:bold>5\u20138<\/jats:bold>\n                    ) in vitro. The structural elucidation was performed with the usage of IR, \u00b9H\u2010NMR and \u00b9\u00b3C\u2010NMR. Compounds\n                    <jats:bold>6b<\/jats:bold>\n                    and\n                    <jats:bold>8b<\/jats:bold>\n                    had significant anti\u2010cytotoxic activity in the MCF\u20107 cell line and had IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 5.316\u2009\u00b5g\/mL and 2.805\u2009\u00b5g\/mL where they had minimal toxicity on normal cells (MCF\u201010A). The mechanistic studies have shown that compound\n                    <jats:bold>6b<\/jats:bold>\n                    and\n                    <jats:bold>8b<\/jats:bold>\n                    were very effective in stopping the cell cycle at the G1 stage and also the induction of apoptosis. Moreover, the compounds\n                    <jats:bold>6b<\/jats:bold>\n                    and\n                    <jats:bold>8b<\/jats:bold>\n                    depicted in the paper displayed an inhibitory action concerning the aromatase enzyme. The results of qRT\u2010PCR implied that both compounds\n                    <jats:bold>6b<\/jats:bold>\n                    and\n                    <jats:bold>8b<\/jats:bold>\n                    exerted a considerable apoptotic impact in the manner in which they up\u2010regulated caspase\u20109 and p53 and down\u2010regulated Bcl\u20102. The binding interaction mechanisms between the docked compounds and aromatase enzyme and Bcl\u20102 receptors were better understood in terms of a molecular docking analysis. Altogether, the results of the present study suggest that the 1, 3, 5\u2010trisubstituted\u20102\u2010thioxo\u2010imidazole backbone can be used as a promising new scaffold in future development of multi\u2010action anti\u2010cancer drugs in breast cancer.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70243","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T13:53:14Z","timestamp":1770990794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovery of Novel 1,3,5\u2010trisubstituted\u20102\u2010thioxo\u2010imidazole Derivatives as Potential Aromatase Inhibitors: Design, Synthesis, In Vitro Anti\u2010Breast Cancer Screening and Molecular Docking Studies"],"prefix":"10.1002","volume":"87","author":[{"given":"Mohamed F.","family":"Youssef","sequence":"first","affiliation":[{"name":"Chemistry Department, Faculty of Science Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jehan A.","family":"Hasanen","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa A.","family":"Shehata","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman M.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9008-8269","authenticated-orcid":false,"given":"Youstina William","family":"Rizzk","sequence":"additional","affiliation":[{"name":"Chemistry Department (Division of Biochemistry), Faculty of Science Port Said University Port Said Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza M.","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2025.143705"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3987\/com-22-14652"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2009.05.043"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.S307113"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7MD00067G"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11243-012-9634-z"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-013-0879-6"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.113115"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2022.08.010"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c04384"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/go.23.00439"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107607"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2025.106729"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/17568919.2024.2366694"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24744"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-9-41"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2023.134920"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115581"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.133942"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.111815"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07614"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-76533-4"},{"issue":"1","key":"e_1_2_7_24_1","first-page":"43","article-title":"Synthesis, Spectral Characterization, DFT Calculations and Investigation of Anticancer Properties of Carbothioamide and Metal (FeII and CrIII) complexes","volume":"64","author":"Gueney E.","year":"2025","journal-title":"Indian Journal of Chemistry (IJC)"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-16-8399-2_6"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11164-024-05354-x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29020346"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520620666200705214917"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12207"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.4791"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00404-3"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202104333"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202100580"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30102245"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13221838"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2NJ00424K"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/13895575113136660091"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202401797"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2018-0468"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2025.110308"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1039\/d3ra04182d"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA02944E"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26144213"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.2174\/0109298673305163240427065543"},{"key":"e_1_2_7_45_1","first-page":"44","article-title":"Divers Pharmacological Significance of Imidazole Derivatives\u2014A Review","volume":"6","author":"Shrivastava T. P.","year":"2013","journal-title":"Research Journal of Pharmacy and Technology"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13065-023-01014-0"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"issue":"22","key":"e_1_2_7_48_1","first-page":"8037","article-title":"Signaling Pathways of Apoptosis Activated by Aromatase Inhibitors and Antiestrogens","volume":"63","author":"Thiantanawat A.","year":"2003","journal-title":"Cancer Research"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40487-025-00346-2"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/329412"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA05014B"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2021.132496"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-022-00468-0"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21290"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10600-025-04632-3"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70243","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ddr.70243","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70243","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T17:42:35Z","timestamp":1786038155000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.70243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,13]]},"references-count":54,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/ddr.70243"],"URL":"https:\/\/doi.org\/10.1002\/ddr.70243","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,13]]},"assertion":[{"value":"2025-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70243"}}