{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T12:04:52Z","timestamp":1794485092050,"version":"4.9.1"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["ORF\u2010RC\u20102025\u20100121"],"award-info":[{"award-number":["ORF\u2010RC\u20102025\u20100121"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001774","name":"University of Sydney","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A novel series of triazole hydrazide derivatives\n                    <jats:bold>8a\u2010o<\/jats:bold>\n                    was rationally designed, synthesized, and systematically evaluated for their anticancer potential. Cytotoxicity screening against A549 lung adenocarcinoma cells identified compounds\n                    <jats:bold>8a\u2010d<\/jats:bold>\n                    as the most potent, exhibiting IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 3.15\u20134.93\u2009\u00b5M, which are comparable to doxorubicin (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20092.77\u2009\u00b5M). Mechanistic studies revealed that lead compound\n                    <jats:bold>8a<\/jats:bold>\n                    induced apoptosis through upregulation of Bax and caspase\u20103 and downregulation of Bcl\u20102. Additionally,\n                    <jats:bold>8a<\/jats:bold>\n                    significantly inhibited A549 cell migration (34.46% wound closure vs. 61.61% in controls) and reduced clonogenic survival (surviving fraction = 0.5725). Importantly,\n                    <jats:bold>8a<\/jats:bold>\n                    displayed low cytotoxicity toward normal lung fibroblasts (WI\u201038, IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200947.21\u2009\u00b5M). Enzyme inhibition assays demonstrated potent EGFR kinase inhibition by\n                    <jats:bold>8a<\/jats:bold>\n                    and\n                    <jats:bold>8\u2009d<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200974.85 and 75.87\u2009nM, respectively), comparable to erlotinib (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200934.89\u2009nM). Moreover,\n                    <jats:italic>in silico<\/jats:italic>\n                    ADMET profiling predicted favorable drug\u2010likeness and oral bioavailability, while molecular docking supported the stable binding of\n                    <jats:bold>8a<\/jats:bold>\n                    within the EGFR active site. These findings identify compound\n                    <jats:bold>8a<\/jats:bold>\n                    as a promising therapeutic lead for the development of targeted EGFR inhibitors in non\u2010small cell lung cancer (NSCLC) therapy.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70211","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:16:17Z","timestamp":1765977377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Rational Design of Triazole Hydrazide Derivatives With Imidazo[2,1\u2010\n                    <i>b<\/i>\n                    ]thiazole Scaffolds as Targeted EGFR Inhibitors in NSCLC"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8269-9526","authenticated-orcid":false,"given":"Mohamed K.","family":"Elgohary","sequence":"first","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Egyptian Russian University Badr City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud S.","family":"Elkotamy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Alsalam University Kafr El Zayat Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab M.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Scientific Research and Innovation Support Unit, Faculty of Pharmacy Kafrelsheikh University Kafrelsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrar mortada","family":"abdelraheem","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Egyptian Russian University Badr City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim Taha","family":"Radwan","sequence":"additional","affiliation":[{"name":"Supplementary General Sciences Department, Faculty of Oral and Dental Medicine Future University in Egypt Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4366-6200","authenticated-orcid":false,"given":"Eman","family":"Darweish","sequence":"additional","affiliation":[{"name":"Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy Egyptian Russian University Badr City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8711-3873","authenticated-orcid":false,"given":"Abdulrahman A.","family":"Almehizia","sequence":"additional","affiliation":[{"name":"Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4377-5239","authenticated-orcid":false,"given":"Ahmed M.","family":"Naglah","sequence":"additional","affiliation":[{"name":"Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad A.","family":"Almehizia","sequence":"additional","affiliation":[{"name":"Dental department Prince Mohammed bin Abdulaziz Hospital Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Fares","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy Egyptian Russian University Badr City Egypt"},{"name":"School of Pharmacy The University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-4017","authenticated-orcid":false,"given":"Wagdy M.","family":"Eldehna","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Kafrelsheikh University Kafrelsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem A.","family":"Abdel\u2010Aziz","sequence":"additional","affiliation":[{"name":"Applied Organic Chemistry Department National Research Center Dokki Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202300244"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.108159"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202100158"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17020216"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116698"},{"key":"e_1_2_11_7_1","unstructured":"Articles Burden of Disease Scenarios for 204 Countries and Territories 2022\u20102050: A Forecasting Analysis for the Global Burden of Disease Study 2021.2024.www.thelancet.com."},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.103811"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13896"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2008.06.019"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116727"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171385"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.137803"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2004.06.007"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BMC.2007.03.044"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2023.2175209"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.142372"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107393"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/17568919.2025.2561543"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.140579"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107766"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106724"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117752"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.108565"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.108247"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.117158"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17010081"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107626"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3791\/50767"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.58"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-9140(03)00238-8"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e23172"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2018.1555156"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117340"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2008.05.028"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28196950"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113616"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.06.031"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105164"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules181011683"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/7651_2019_259"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.108702"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.38793"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121513"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm400072p"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104133"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.108153"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0md00188k"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2018.09.008"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90034-5"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2025.130096"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01078-2"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2022.119317"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/clr.14067"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2007.10.005"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2014.09.037"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70211","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ddr.70211","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70211","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T09:56:54Z","timestamp":1769853414000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.70211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,17]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/ddr.70211"],"URL":"https:\/\/doi.org\/10.1002\/ddr.70211","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,17]]},"assertion":[{"value":"2025-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70211"}}