Scaffold-Hopping Design and Synthesis of Thieno[3,2-]pyrimidines: Anticancer Activity, Apoptosis Induction, and In Silico Inhibition of CDKs.

Two series of tricyclic thieno[3,2-]pyrimidines were synthesized, achieving yields of up to 97%. The tricyclic thieno[3,2-]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-]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 is likely to disrupt the cell cycle process through targeting CDKs (Cyclin-dependent kinases), leading to the inhibition of tumor cell proliferation.