New pyrimidine compounds as potent anti-breast cancer agents: synthesis, biological evaluation and computational studies.

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, highlighting the urgent need for novel therapeutic agents. In this study, a series of pyrimidine-based derivatives were designed and synthesized to evaluate their potential as anti-breast cancer agents. The compounds were screened for anti-proliferative activity against MDA-MB-231 breast cancer cells, and selected candidates were further assessed for CDK2 inhibitory potential. Among the synthesized compounds, 7b (IC₅₀ = 4.21 ± 0.62 μM) and 7d (IC₅₀ = 5.16 ± 0.71 μM) exhibited potent cytotoxicity and induced apoptosis, with 7d also demonstrating significant CDK2 inhibition. Computational studies, including molecular docking, molecular dynamics simulations, and binding energy analyses, revealed stable interactions within the CDK2 active site. Additionally, ADMET predictions indicated favorable pharmacokinetic and drug-like properties. Overall, these findings suggest that pyrimidine-based compounds, particularly 7b and 7d, possess promising anti-proliferative properties, with CDK2 inhibition contributing to their mechanism of action and supporting their potential as lead candidates for breast cancer therapy.