Abstract
<jats:p>A number of uracil amides are known PARP inhibitors in cancer, prompting the design and synthesis of novel thiouracil amide derivatives for potential breast cancer therapy. Several newly synthesized compounds, particularly Compound 5a and 5b, exhibited moderate to significant efficacy in estrogen-receptor-positive MCF-7 breast cancer cells (IC₅₀ as low as 18 μM). These amides inhibited PARP1 catalytic activity, promoted PARP1 cleavage, increased H2AX phosphorylation, and activated Caspase 3/7, indicating induction of apoptosis. Density functional theory and molecular docking confirmed the stable binding of lead compounds in the PARP1 active site. The findings highlight these thiouracil amides as promising candidates for oncological PARP inhibition and it is published in molecules journal.</jats:p>