New Barbituric Acid–Triazole Derivatives as CDK Inhibitors and as Promising Agents Against Breast Cancer Cell Line: Synthesis and Computational Studies

We derived a new series of barbituric acid-1,2,3-triazole hybrids (9a–9j) using Cu(I)-catalyzed azide–alkyne cycloaddition, and traditional spectroscopic methods have been used to study them. The compounds were tested for their ability to kill cells in vitro by using the MCF-7 human breast cancer cell line and for their ability to stop the biological function of cyclin-dependent kinase 2 (CDK2). Biological findings indicated a moderate impact of phenyl ring substitution on activity. Compounds containing electron-withdrawing groups, especially 9g (4-CF 3 ) and 9h (4-F), were very effective at inhibiting CDK2, with IC 50 values of 3.12 and 4.20 µM, respectively. Compound 9e (4-Me) exhibited the maximum cytotoxicity against MCF-7 cells (IC 50 = 2.02 µM), followed by compounds 9g and 9b. Structure–activity relationship research revealed that both electronic and hydrophobic effects at the para-position substantially affect activity. Molecular docking investigations corroborated these findings, illustrating advantageous interactions of active chemicals within the ATP-binding pocket of CDK2.