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Density functional theory (DFT) calculations, including frontier molecular orbital (FMO) analysis and global reactivity descriptors, supported the preferential formation of the E\u2010isomeric forms. In silico target prediction prioritized cyclin\u2010dependent kinase 2 (CDK2), and molecular docking of representative active members (\n                    <jats:bold>4b, 4\u2009d, 4p,<\/jats:bold>\n                    and\n                    <jats:bold>4r<\/jats:bold>\n                    ) revealed key contacts around Arg83\/Pro84 and favorable binding energies (\u2009\u2212\u20093.91 to \u22126.20\u2009kcal\/mol). In vitro antiproliferative activity against human colon carcinoma (HCT\u2010116) and human hepatocellular carcinoma (HepG2) cell lines identified\n                    <jats:bold>4r<\/jats:bold>\n                    as the most potent compound (half\u2010maximal inhibitory concentration, IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20095.26\u2009\u00b1\u20090.37 and 5.03\u2009\u00b1\u20090.42\u2009\u00b5M, respectively), surpassing doxorubicin (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20097.05\u2009\u00b1\u20090.49 and 6.42\u2009\u00b1\u20090.31\u2009\u00b5M). Absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction indicated high gastrointestinal (GI) absorption, no blood\u2013brain barrier (BBB) permeation, no P\u2010glycoprotein (P\u2010gp) substrate liability, a bioavailability score of 0.55, and zero pan\u2010assay interference compounds (PAINS) alerts. Overall, the integrated synthetic, computational, and biological results highlight azine\u2010linked thiazolo[3,2\u2010a]benzimidazoles, particularly\n                    <jats:bold>4r<\/jats:bold>\n                    , as promising CDK2\u2010directed anticancer leads.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70272","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:54:36Z","timestamp":1775109276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Design, Synthesis, In Silico Profiling, and In Vitro Anticancer Assessment of Azine\u2010Linked Thiazolo[3,2\u2010a]benzimidazoles as CDK2\u2010Directed Therapeutic Candidates"],"prefix":"10.1002","volume":"87","author":[{"given":"Mohamed S. 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A.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Imam Mohammad Ibn Saud Islamic University (IMSIU) Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9372-9364","authenticated-orcid":false,"given":"Suzan","family":"Alhilal","sequence":"additional","affiliation":[{"name":"Department of Medical Services and Techniques, Vocational School of Health Services Mardin Artuklu University Mardin Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8799-0235","authenticated-orcid":false,"given":"Mohamed","family":"El\u2010Naggar","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Pure and Applied Chemistry Group, Faculty of Sciences University of Sharjah Sharjah UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesam","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Islamic University of Madinah Madinah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2893-0376","authenticated-orcid":false,"given":"Ahmed A.","family":"Elhenawy","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science Al Baha University Al Baha Saudi Arabia"},{"name":"Chemistry Department, Faculty of Science Al\u2010Azhar University Nasr City Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sobhi M.","family":"Gomha","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Islamic University of Madinah Madinah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30949"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1134\/S1070363225602066"},{"key":"e_1_2_9_4_1","unstructured":"Abdel\u2010Rahman A. 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