Background: It was found that breast cancer susceptibility protein 1 (BRCA 1) binds to estrogen receptor alpha (ERα) and inhibits its activity by direct interaction between domains within the amino terminus of BRCA 1 and the carboxy terminus of ER alpha.

Objectives: The present work focuses to identify a new class of BRCA 1 mimetics that work differently from conventional anti-estrogens.

Methods: A novel class of hybrids having coumate and benzimidazolone scaffolds were designed to mimic BRCA 1 protein, suppressing the tumor activity of breast cancer cells. In silico molecular docking studies of the designed ligands were performed on BRCA 1 binding cavity of ER alpha.

Results: The designed hybrids which gave significant docking scores and had optimum binding interactions with key residues were selected for synthesis and in vitro assay.

Conclusion: The compounds NY1 and NY2 exhibited significant effects on suppressing MDAMB- 231 cells in the concentration of 24 μg/ml and 44 μg/ml, respectively.

背景：发现乳腺癌易感蛋白 1 (BRCA 1) 与雌激素受体 α (ERα) 结合，并通过 BRCA 1 氨基末端和 ER α 羧基末端内的结构域之间的直接相互作用抑制其活性。

目标：目前的工作重点是确定一类新的 BRCA 1 模拟物，其作用不同于传统的抗雌激素。

方法：设计了一类具有香豆酸盐和苯并咪唑酮支架的新型杂交体来模拟 BRCA 1 蛋白，抑制乳腺癌细胞的肿瘤活性。在 ER α 的 BRCA 1 结合腔上进行了设计配体的计算机分子对接研究。

结果：选择了具有显着对接分数并与关键残基具有最佳结合相互作用的设计杂合体用于合成和体外测定。

结论：化合物NY1和NY2分别在24 μg/ml和44 μg/ml的浓度下对MDAMB-231细胞表现出显着的抑制作用。