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The tricyclic thieno[3,2-d]pyrimidines examined in this study are synthetic analogs of the deoxyvasicinone alkaloids, where the thiophene ring substitutes for the benzene ring. A systematic investigation was conducted on the scaffold-hopping strategy of these alkaloids, emphasizing the selective synthesis and anticancer properties of thieno[3,2-d]pyrimidines. The anticancer evaluation was performed on human cancer cell lines, specifically cervical HeLa and colon HT-29 carcinoma cells. Additional bioassays included cell migration analyses, cell cycle progression, apoptosis, and molecular docking analyses. Furthermore, molecular docking studies showed that the most active small molecule 6e is likely to disrupt the cell cycle process through targeting CDKs (Cyclin-dependent kinases), leading to the inhibition of tumor cell proliferation.<\/jats:p>","DOI":"10.3390\/ijms26178528","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Scaffold-Hopping Design and Synthesis of Thieno[3,2-d]pyrimidines: Anticancer Activity, Apoptosis Induction, and In Silico Inhibition of CDKs"],"prefix":"10.3390","volume":"26","author":[{"given":"Zukela","family":"Ruzi","sequence":"first","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China"},{"name":"School of Chemistry and Chemical Engineering, Changji University, Changji 831100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1887-6804","authenticated-orcid":false,"given":"Anvarjon","family":"Buronov","sequence":"additional","affiliation":[{"name":"Department of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifei","family":"Nie","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azizbek","family":"Nasrullaev","sequence":"additional","affiliation":[{"name":"Department of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarifa","family":"Murtazaeva","sequence":"additional","affiliation":[{"name":"Department of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9665-9982","authenticated-orcid":false,"given":"Rustamkhon","family":"Kuryazov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Urgench State University, Kh. 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