{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:46:12Z","timestamp":1791377172859,"version":"4.3.2"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In this study, a novel series of chromene\u2010based derivatives was rationally designed as potential VEGFR\u20102 inhibitors based on key structural and pharmacophoric features required for antiangiogenic activity. Accordingly, twelve chromene derivatives (\n                    <jats:bold>13a\u2013e, 15a\u2013e<\/jats:bold>\n                    , and\n                    <jats:bold>17a\u2013b<\/jats:bold>\n                    ) were successfully synthesized and structurally characterized. The synthesized compounds were evaluated in vitro for their cytotoxic activity against human cancer cell lines (MCF\u20107, HepG\u20102, and HCT\u2010116), in addition to normal WI\u201038 and WISH cells. Among the tested compounds, compound\n                    <jats:bold>13a<\/jats:bold>\n                    demonstrated the most potent and selective antiproliferative activity, exhibiting low micromolar IC\n                    <jats:sub>50<\/jats:sub>\n                    values and favorable selectivity indices. Enzymatic assays confirmed its VEGFR\u20102 inhibitory activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20091.666\u2009\u00b1\u20090.025\u2009\u00b5M), comparable to the reference drug sorafenib. Mechanistic investigations revealed that compound\n                    <jats:bold>13a<\/jats:bold>\n                    effectively inhibited cancer cell migration in a wound healing assay, highlighting its potential antiangiogenic properties. Furthermore, compound\n                    <jats:bold>13a<\/jats:bold>\n                    induced significant G0\/G1 cell cycle arrest in MCF\u20107 cells and triggered apoptosis, as evidenced by Annexin V\/PI staining. To support the experimental findings, Density Functional Theory (DFT) calculations confirmed favorable structural stability and electronic properties. Molecular docking studies demonstrated strong binding interactions within the VEGFR\u20102 ATP\u2010binding site. These results were further validated by 200\u2009ns molecular dynamics simulations, MM\u2010GBSA binding free energy calculations, Protein\u2013Ligand Interaction Fingerprints (Pro\u2010LIF), Principal Component Analysis of Trajectories (PCA\u2010T), and Free Energy Landscape (FEL) analyses, confirming the dynamic stability and favorable energetics of the VEGFR\u20102\u2013\n                    <jats:bold>13a<\/jats:bold>\n                    complex. Overall, this integrated experimental and computational study identifies compound\n                    <jats:bold>13a<\/jats:bold>\n                    as a promising VEGFR\u20102\u2013targeted anticancer lead warranting further preclinical investigation.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70297","type":"journal-article","created":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T21:01:21Z","timestamp":1777842081000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Structure\u2010Guided Design and Mechanistic Elucidation of New Chromene Derivatives as Selective Vascular Endothelial Growth Factor Receptor\u20102 Inhibitors With Potent Anticancer Activity"],"prefix":"10.1002","volume":"87","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 Pharmacy (Boys) Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5982-5635","authenticated-orcid":false,"given":"Walid E.","family":"Elgammal","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Science Al\u2010Azhar University, Nasr City 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 University 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\/0000-0003-4497-5013","authenticated-orcid":false,"given":"Aisha A.","family":"Alsfouk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy Princess Nourah bint Abdulrahman University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2615-7375","authenticated-orcid":false,"given":"Fatma G.","family":"Amin","sequence":"additional","affiliation":[{"name":"Physics Department Faculty of Science Alexandria University Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7552-0914","authenticated-orcid":false,"given":"Dalal Z.","family":"Husein","sequence":"additional","affiliation":[{"name":"Chemistry Department Faculty of Science New Valley University El\u2010Kharja Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-1980","authenticated-orcid":false,"given":"Ahmed M.","family":"Metwaly","sequence":"additional","affiliation":[{"name":"Pharmacognosy and Medicinal Plants Department Faculty of Pharmacy (Boys) Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2546-8035","authenticated-orcid":false,"given":"Eslam B.","family":"Elkaeed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry Faculty of Pharmacy (Boys) Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1NJ02710G"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.podrm.2018.11.003"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-016-0352-8"},{"issue":"3","key":"e_1_2_14_5_1","first-page":"589","article-title":"Feasibility of Drug Screening With Panels of Human Tumor Cell Lines Using a Microculture Tetrazolium Assay","volume":"48","author":"Alley M. 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