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DFT experiments was utilized also to study the structural and electrostatic properties of <jats:bold>T-1-NBAB<\/jats:bold>. Computational analysis was performed to predict the ADME-Tox profiles of <jats:bold>T-1-NBAB<\/jats:bold>. After semisynthesis, the <jats:italic>in vitro<\/jats:italic> results showed that <jats:bold>T-1-NBAB<\/jats:bold> effectively inhibits VEGFR-2, with an IC<jats:sub>50<\/jats:sub> of 0.115 \u03bcM, compared to sorafenib\u2019s 0.0591 \u03bcM. <jats:italic>In vitro<\/jats:italic> tests also demonstrated significant activity of <jats:bold>T-1-NBAB<\/jats:bold> against breast cancer cell lines MCF7 and T47D, with IC<jats:sub>50<\/jats:sub> values of 16.88 \u03bcM and 61.17 \u03bcM, respectively, and high selectivity. Importantly, <jats:bold>T-1-NBAB<\/jats:bold> induced early and late apoptosis in MCF7 cells, indicating its potential as a strong anticancer agent. Additionally, <jats:bold>T-1-NBAB<\/jats:bold> reduced the migration and healing abilities of MCF7 cells, suggesting it could be a promising anti-angiogenic agent. Overall, these findings suggest that <jats:bold>T-1-NBAB<\/jats:bold> is a promising lead compound for further research as a potential treatment for breast cancer.<\/jats:p>","DOI":"10.1371\/journal.pone.0316146","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T18:40:12Z","timestamp":1738003212000},"page":"e0316146","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrated in silico and in vitro exploration of the anti-VEGFR-2 activities of a semisynthetic xanthine alkaloid inhibiting breast cancer"],"prefix":"10.1371","volume":"20","author":[{"given":"Eslam B.","family":"Elkaeed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0893-6703","authenticated-orcid":true,"given":"Hazem","family":"Elkady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Khattab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reda G.","family":"Yousef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan A.","family":"Al-ghulikah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalal Z.","family":"Husein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim M.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Elkady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8566-1980","authenticated-orcid":true,"given":"Ahmed M.","family":"Metwaly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim H.","family":"Eissa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"pone.0316146.ref001","unstructured":"International W. 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