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Several derivatives demonstrated broad-spectrum growth inhibition, with compounds\n                    <jats:bold>10b<\/jats:bold>\n                    ,\n                    <jats:bold>11a<\/jats:bold>\n                    , and\n                    <jats:bold>11b<\/jats:bold>\n                    emerging as the most active candidates, exhibiting mean GI\u2085\u2080 values in the low micromolar range (4.36\u201316.4 \u00b5M). A deeper biological assessment revealed that these hybrids act as dual inhibitors of EGFR and VEGFR-2, with compound\n                    <jats:bold>11b<\/jats:bold>\n                    showing the highest potency (IC\u2085\u2080 = 26.38 nM and 114.17 nM, respectively). Mechanistic studies further confirmed that\n                    <jats:bold>11b<\/jats:bold>\n                    induced G2\/M phase arrest and triggered apoptotic pathways in MCF-7 cells. The oxime-containing analogs exhibited enhanced nitric oxide (NO) release, a property associated with modulation of angiogenesis and increased susceptibility of cancer cells to apoptosis, contributing to their observed anticancer activity. Molecular docking and structure\u2013activity relationship analysis clarified the binding interactions and substitution patterns governing activity, and both cytotoxicity and mechanistic analyses converged on compound\n                    <jats:bold>11b<\/jats:bold>\n                    as the most promising lead of the series.\n                  <\/jats:p>","DOI":"10.1007\/s11030-025-11411-3","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T11:34:48Z","timestamp":1768995288000},"page":"4667-4699","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel pyrazole\u2013oxadiazole\u2013chalcone\/oxime hybrids as dual EGFR\/VEGFR-2 inhibitors with promising anticancer potential: a comprehensive cytotoxicity evaluation, mechanistic insights and SAR analysis"],"prefix":"10.1007","volume":"30","author":[{"given":"Omar","family":"Alshazly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abdel-Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal El-Din A.","family":"Abuo-Rahma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamdouh F. 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