{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:07:38Z","timestamp":1790690858787,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2026R116"],"award-info":[{"award-number":["PNURSP2026R116"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A new series of chromene derivatives (\n                    <jats:bold>12\u201319<\/jats:bold>\n                    ) was rationally designed as potential inhibitors of vascular endothelial growth factor receptor\u20102 (VEGFR\u20102) by integrating essential pharmacophoric and structural features. The target compounds were synthesized and structurally confirmed using spectroscopic techniques. Their in vitro antiproliferative activities were evaluated against a panel of human cancer cell lines (MCF\u20107, MDA\u2010MB\u2010231, HepG\u20102, and HCT\u2010116) alongside normal human cells (WI\u201038 and WISH), in addition to a VEGFR\u20102 enzyme inhibition assay. Among the synthesized derivatives, compound\n                    <jats:bold>17<\/jats:bold>\n                    emerged as the most potent candidate, displaying low micromolar IC\n                    <jats:sub>50<\/jats:sub>\n                    values across all tested cancer cell lines and superior VEGFR\u20102 inhibitory activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.518\u2009\u00b5M) compared with the reference drug sorafenib (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.809\u2009\u00b5M). Mechanistic investigations revealed that compound\n                    <jats:bold>17<\/jats:bold>\n                    induced pronounced cell cycle arrest and triggered apoptosis, as demonstrated by Annexin V\u2013FITC\/PI flow cytometric analysis. Computationally, Density Functional Theory (DFT) calculations demonstrated favorable electronic properties for compound\n                    <jats:bold>17,<\/jats:bold>\n                    supporting effective ligand\u2013receptor interactions. Molecular docking and 100\u2010ns molecular dynamics (MD) simulations, complemented by MM\u2010GBSA binding free energy calculations, Protein\u2013Ligand Interaction Fingerprinting (Pro\u2010LIF), Principal Component Analysis (PCA\u2010T), and Free Energy Landscape (FEL) analyses, confirmed the stability and favorable binding energetics of compound\n                    <jats:bold>17<\/jats:bold>\n                    within the VEGFR\u20102 active site. Furthermore, in silico ADME\u2013Tox profiling predicted acceptable pharmacokinetic behavior and a favorable safety profile. Collectively, these experimental and computational findings identify compound\n                    <jats:bold>17<\/jats:bold>\n                    as a promising and mechanistically well\u2010characterized VEGFR\u20102 inhibitor, warranting further in vivo investigation.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70328","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:55:54Z","timestamp":1789023354000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New Chromene Derivatives as Promising VEGFR\u20102 Inhibitors: Experimental Cytotoxicity and Comprehensive Computational Characterization"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0893-6703","authenticated-orcid":false,"given":"Hazem","family":"Elkady","sequence":"first","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry &amp; Drug Design Department, Faculty of 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Al\u2010Azhar University Nasr City Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6620-241X","authenticated-orcid":false,"given":"Hazem A.","family":"Mahdy","sequence":"additional","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry &amp; Drug Design Department, Faculty of Pharmacy (Boys) Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1820-9684","authenticated-orcid":false,"given":"Ahmed","family":"Nofal","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6955-2263","authenticated-orcid":false,"given":"Ibrahim H.","family":"Eissa","sequence":"additional","affiliation":[{"name":"Pharmaceutical Medicinal Chemistry &amp; Drug Design Department, Faculty of Pharmacy (Boys) Al\u2010Azhar 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