Abstract

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-CF3) and 9h (4-F), were very effective at inhibiting CDK2, with IC50 values of 3.12 and 4.20 µM, respectively. Compound 9e (4-Me) exhibited the maximum cytotoxicity against MCF-7 cells (IC50 = 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.

Key words: Barbituric acid–triazole hybrids, CDK-2 inhibition, MCF-7 breast cancer cells, Structure–activity relationship (SAR), Molecular docking.