Background: Coumarin is a fused ring system and possesses the enormous capability of targeting various receptors participating in the cancer pathway. Coumarin and its derivatives were found to exhibit very rare toxicity and other side effects. It has been found its immense anticancer potential depends on the nature of the group present and its pattern of substitution on the basic nucleus.

Objectives: Synthesis of C-4 substituted coumarin derivatives and to study their molecular interactions with ERα for the anticancer activity for Breast Cancer.

Methods: C-4 substituted coumarins analogues (1-10) have been synthesized using conventional heating and microwave irradiation. Using Schrodinger software, molecular modeling studies were carried out and ADME properties of the compounds were predicted.

Results: All the synthesized compounds have shown better G-Score (-6.87 to -8.43 kcal/mol) as compared to the standard drug tamoxifen (-5.28kcal/mol) and auraptene (-3.89kcal/mol). Molecular docking suggests that all compounds fit in the active site of protein as they have the same hydrophobic pocket as standard drug tamoxifen, and have an acceptable range of ADME properties.

Conclusion: Microwave-assisted synthesis showed better results as compared to conventional heating. In silico studies revealed that all the compounds befit in the active site of the protein. ADME properties showed that all compounds are in allowable limits for human oral absorption. In the future, there is a possibility of in vitro and in vivo studies of the synthesized compounds.

背景：香豆素是一种稠环系统，具有靶向参与癌症通路的各种受体的巨大能力。发现香豆素及其衍生物表现出非常罕见的毒性和其他副作用。已经发现其巨大的抗癌潜力取决于存在的基团的性质及其在基本核上的取代模式。

目的：合成 C-4 取代的香豆素衍生物，并研究它们与 ERα 的分子相互作用，用于乳腺癌的抗癌活性。

方法：使用常规加热和微波辐射合成了 C-4 取代香豆素类似物 (1-10)。使用薛定谔软件进行分子建模研究并预测化合物的 ADME 特性。

结果：与标准药物他莫昔芬（-5.28kcal/mol）和奥拉普汀（-3.89kcal/mol）相比，所有合成的化合物都显示出更好的G-Score（-6.87至-8.43 kcal/mol）。分子对接表明所有化合物都适合蛋白质的活性位点，因为它们具有与标准药物他莫昔芬相同的疏水口袋，并且具有可接受的 ADME 特性范围。

结论：与传统加热相比，微波辅助合成显示出更好的结果。计算机研究表明，所有化合物都适合蛋白质的活性位点。ADME 特性表明，所有化合物都在人类口服吸收的允许限度内。将来，有可能对合成的化合物进行体外和体内研究。