{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:49:33Z","timestamp":1791560973207,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The epidermal growth factor receptor (EGFR) family is a key biomarker and therapeutic target for cancer therapy. Although acridone scaffolds have previously inhibited other tyrosine kinases, their specific targeting of EGFR has not been reported. This study provides novel acridone\u2010N\u2010aceto\/benzohydrazide derivatives with anti\u2010EGFR activity. Cytotoxicity screening revealed\n                    <jats:bold>AE4<\/jats:bold>\n                    ,\n                    <jats:bold>AE11<\/jats:bold>\n                    , and\n                    <jats:bold>AF11<\/jats:bold>\n                    as highly effective against the A\u2010431 cell line, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values 3.22\u2009\u00b5M, 2.43\u2009\u00b5M, and 4.06\u2009\u00b5M, respectively, keeping Erb as a standard with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 1.62\u2009\u00b5M. In vitro EGFR kinase assays confirmed their inhibition, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 3.95\u2009\u00b5M (\n                    <jats:bold>AE4<\/jats:bold>\n                    ), 3.49\u2009\u00b5M (\n                    <jats:bold>AE11<\/jats:bold>\n                    ), and 4.45\u2009\u00b5M (\n                    <jats:bold>AF11<\/jats:bold>\n                    ), selectively reduced p\u2010EGFR Tyr\n                    <jats:sup>1068<\/jats:sup>\n                    and ERK1\/2 levels in a dose\u2010dependent manner, while inducing G\n                    <jats:sub>0<\/jats:sub>\n                    \/G\n                    <jats:sub>1<\/jats:sub>\n                    cell\u2010cycle arrest and apoptosis. SAR indicates isopropyl substitutions on the phenyl ring and 2\u2010methoxy on the acridone ring are important for anti\u2010proliferative activity. Notably,\n                    <jats:bold>AE4<\/jats:bold>\n                    exhibited a high DNA\u2010binding affinity (K\n                    <jats:sub>b<\/jats:sub>\n                    \u2009=\u20097.41\u2009\u00d7\u200910\n                    <jats:sup>3<\/jats:sup>\n                    M\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>1<\/jats:sup>\n                    ), suggesting that its efficacy might be due to DNA intercalation. In contrast,\n                    <jats:bold>AE11<\/jats:bold>\n                    and\n                    <jats:bold>AF11<\/jats:bold>\n                    demonstrated significant cytotoxicity, implying the involvement of the RAS\/ERK downregulating pathway. Molecular docking indicated favorable EGFR active site interactions. In silico studies predicted oral bioavailability and low toxicity, supported by kinetic solubility and plasma stability assays, highlighting their potential as selective p\u2010EGFR Tyr\n                    <jats:sup>1068<\/jats:sup>\n                    inhibitors for further development.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70354","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:57:44Z","timestamp":1791557864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Acridone\u2010Based EGFR Inhibitors: Design, Synthesis, and Integrated In Silico\u2013In Vitro Evaluation"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8173-0674","authenticated-orcid":false,"given":"Nilam","family":"Bhusare","sequence":"first","affiliation":[{"name":"Somaiya Institute for Research and Consultancy Somaiya Vidyavihar University, Vidyavihar 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