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The approach provided outstanding yields and adheres to sustainable chemical principles. Analysis revealed CDK4 as a possible therapeutic target linked to breast cancer growth, therefore elucidating its biological potential. In silico molecular docking validated the robust binding affinities of the synthesized derivatives to the CDK4 active site, especially compound\n                    <jats:bold>4<\/jats:bold>\n                    , which demonstrated the greatest interaction energy and stable orientation inside the binding pocket. In vitro cytotoxic studies on MCF\u20107 and MDA\u2010MB\u2010231 breast cancer cell lines demonstrated that compound\n                    <jats:bold>4<\/jats:bold>\n                    had the highest antiproliferative activity (IC\u2085\u2080 = 5.80 and 6.44\u2009\u00b5M, respectively), equivalent to doxorubicin and sorafenib. Compound\n                    <jats:bold>3<\/jats:bold>\n                    had significant effects, whereas compounds\n                    <jats:bold>9<\/jats:bold>\n                    and\n                    <jats:bold>10<\/jats:bold>\n                    showed modest efficacy. Notably, compound\n                    <jats:bold>4<\/jats:bold>\n                    exhibited little toxicity to WI\u201038 normal fibroblasts (IC\u2085\u2080 = 51.61\u2009\u00b5M), suggesting selectivity for cancer cells. Flow cytometric analyses demonstrated that compound\n                    <jats:bold>4<\/jats:bold>\n                    produced G\u2080\/G\u2081 cell\u2010cycle arrest (82.77%) and initiated apoptosis (35.19%) with little necrosis, therefore validating its CDK4\u2010dependent mechanism. These results together identify compound\n                    <jats:bold>4<\/jats:bold>\n                    as a powerful, selective, and environmentally friendly synthetic CDK4 inhibitor, serving as a viable candidate for the future development of tailored anti\u2010breast cancer therapies.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70322","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:25:16Z","timestamp":1779801916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sustainable One\u2010Pot Synthesis of Novel Triazolopyrimidine Derivatives as Selective CDK4 Inhibitors for Breast Cancer Therapy"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8139-8548","authenticated-orcid":false,"given":"Doaa A.","family":"Elsayed","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5246-3491","authenticated-orcid":false,"given":"Wesam S.","family":"Shehab","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysa M.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Viral Media Lab, Egyptian Organization for Biological Products &amp; Vaccines (VACSERA) Giza Egypt"},{"name":"Department of Medical Laboratory Techniques Al\u2010Farahidi University Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3080-4454","authenticated-orcid":false,"given":"Abdulrahman E.","family":"Mesbah","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gehan T.","family":"El\u2010Bassyouni","sequence":"additional","affiliation":[{"name":"Refractories, Ceramics and Building Materials Department National Research Centre Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar M.","family":"Mousa","sequence":"additional","affiliation":[{"name":"Inorganic Chemistry Department National Research Centre Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia M.","family":"Abo Elenin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed G.","family":"Assy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman S.","family":"Tantawy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","unstructured":"Ablajan K. 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