{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:04:01Z","timestamp":1773025441862,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"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":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Inspired by the structural insights of the reported kinase inhibitor Sorafenib, two new series comprising 19 benzimidazole\u2010based compounds incorporating isatin and thiourea motifs were rationally designed as a novel VEGFR\u20102\u2010targeting anti\u2010cancer chemotype. These compounds were synthesized and evaluated for their anti\u2010cancer activity using the NCI single\u2010dose antiproliferative assay against 60 cancer cell lines. The most potent and broad\u2010spectrum compounds\n                    <jats:bold>8e<\/jats:bold>\n                    ,\n                    <jats:bold>9b<\/jats:bold>\n                    ,\n                    <jats:bold>9d<\/jats:bold>\n                    ,\n                    <jats:bold>9e<\/jats:bold>\n                    ,\n                    <jats:bold>9g<\/jats:bold>\n                    ,\n                    <jats:bold>9h<\/jats:bold>\n                    , and\n                    <jats:bold>9i<\/jats:bold>\n                    were further selected by NCI for the five\u2010dose assay panel. These compounds were then assessed for anti\u2010angiogenic activity against VEGFR\u20102, where compound\n                    <jats:bold>9i<\/jats:bold>\n                    revealed promising activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200958\u2009nM) compared to Sorafenib (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200972\u2009nM), while the rest of the compounds gave an IC\n                    <jats:sub>50<\/jats:sub>\n                    range of 96\u2013981\u2009nM. The most active compound\n                    <jats:bold>9i<\/jats:bold>\n                    showed considerable safety toward normal human WI\u201038 cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200928.847\u2009\u00b5M vs. Sorafenib IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200913.497\u2009\u00b5M) and arrested cell growth in the G1\/S phase with total apoptotic induction of 37.65%. Molecular docking studies revealed favorable binding modes of the designed compounds within the VEGFR\u20102 active site. Molecular dynamics (MD) simulation confirmed the high stability of VEGFR\u20102\u2014\n                    <jats:bold>9i<\/jats:bold>\n                    complex. Physicochemical properties and bioavailability radar plot disclosed adequate drug\u2010likeness properties. Collectively, a new benzimidazole\u2010isatin\/thiourea chemotype was introduced as a promising VEGFR\u20102\u2010targeting anti\u2010cancer scaffold, demonstrating enhanced potency and improved safety relative to Sorafenib, and providing a rational basis for further lead optimization.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70217","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:15:49Z","timestamp":1772964949000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New Benzimidazole Scaffolds Tagged With Isatin\/Thiourea Motifs as Anti\u2010Cancer Agents: Promising Approach for VEGFR\u20102 Inhibition"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5822-5443","authenticated-orcid":false,"given":"Alaa M.","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Mansoura University Mansoura Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-7125","authenticated-orcid":false,"given":"Bhoomendra A.","family":"Bhongade","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry RAK College of Pharmacy, RAK Medical &amp; Health Sciences University Ras Al Khaimah United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samar S.","family":"Tawfik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Mansoura University Mansoura Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed A. M.","family":"Massoud","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Mansoura University Mansoura Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1909-1072","authenticated-orcid":false,"given":"Amany S.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Mansoura University Mansoura Egypt"},{"name":"Pharmacy Center of Scientific Excellence, Faculty of Pharmacy Mansoura University Mansoura Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-653"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.3.505"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0093-7754(02)70065-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(96)10053-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-669"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202100278"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.02.050"},{"key":"e_1_2_9_9_1","article-title":"Identification of Novel Sulfathiazole\u2010triazolo\u2010chalcone Hybrids as VEGFR-2\/EGFR Dual Inhibitors With Antiangiogenic Activity and Apoptotic Induction","author":"Zeidan M. 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