Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current anticancer agents have several drawbacks such as serious side effects and the emergence of resistance to chemotherapeutic drugs. As coumarins possess minimum side effects along with multidrug reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways that can be explored for selective anticancer activity.

Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds for ER-α target protein by molecular docking.

Methods: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17) has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions and ADME study of the compounds were analyzed by using Schrodinger software.

Results: Among the synthesized analogues, 12 and 13 show good antiproliferative activity with IC50 values 1 and 1.3 μM, respectively. Molecular docking suggests a remarkable binding pose of all the seventeen compounds. Compounds 12 and 13 were found to exhibit a docking score of -4.10 kcal/mol and -4.38 kcal/mol, respectively.

Conclusion: Compounds 12 and 13 showed the highest activity followed by 1 and 5. ADME properties of all compounds were in the acceptable range. The active compounds can be taken for lead optimization and mechanistic interventions for their in vivo study in the future.

背景：乳腺癌 (BC) 是继皮肤癌之后女性癌症相关死亡的主要原因。雌激素受体 (ER) 在 BC 的进展中起重要作用。目前的抗癌剂有几个缺点，例如严重的副作用和对化疗药物的耐药性的出现。由于香豆素具有最小的副作用和多药逆转活性，因此它具有调节多种细胞途径的巨大能力，可以探索这些途径的选择性抗癌活性。

目的：合成和评价新香豆素类似物对人乳腺癌细胞系 MCF-7 具有抗增殖活性，并通过分子对接探索化合物与 ER-α 靶蛋白的结合相互作用。

方法：在本研究中，已评估 C-3 取代的香豆素类似物 (1-17) 对雌激素受体阳性 MCF-7 乳腺癌细胞系的抗增殖活性。使用薛定谔软件分析了化合物的分子相互作用和ADME研究。

结果：在合成的类似物中，12 和 13 显示出良好的抗增殖活性，IC50 值分别为 1 和 1.3 μM。分子对接表明所有 17 种化合物都具有显着的结合姿势。发现化合物 12 和 13 的对接分数分别为 -4.10 kcal/mol 和 -4.38 kcal/mol。

结论：化合物12和13的活性最高，其次是1和5。所有化合物的ADME特性均在可接受的范围内。这些活性化合物可用于未来体内研究的先导优化和机械干预。