Background: Breast cancer is the prominent reason of death in women worldwide, and the cases are increasing day by day. There are many FDA-approved drugs for treating breast cancer. Due to drug resistance, and problems in selectivity, there is a need to develop more effective agents with few side effects. Indole derivatives have demonstrated significant pharmacological potential as anti-breast cancer agents. Further, chalcone derivatives incorporating heterocyclic scaffolds play a significant role in medicine. Indole-chalcone-based compounds offer the potential for improved biological activity and enhanced drug-like properties. It prompted us to explore the synthesis of Indole-Chalcone derivatives targeting estrogen receptor alpha (ER-α) to discover potent anti-breast cancer agents. Objectives: To synthesize indole-chalcone derivatives and study their binding interactions for ER-α protein by molecular docking for breast cancer treatment. Methods: In this study, indole-chalcone derivatives have been synthesized using conventional heating. With the help of Schrodinger software, molecular interaction as well as ADME (Adsorption, Distribution, Metabolism, and Excretion) studies of the compounds were conducted. Results: Among all the synthesized compounds, four compounds (1, 2, 3, and 4) showed better docking scores (-10.24 kcal/mol, -10.15 kcal/mol, -9.40 kcal/mol, -9.29 kcal/mol, respectively) than the standard tamoxifen (-8.43 kcal/mol). Conclusion: From In-silico studies, we can conclude that four compounds from the synthesized series fit into the active site of ER-α. ADME properties of synthesized derivatives were found in the acceptable range. In the future, these compounds can be further explored for biological activity.

中文翻译：

---

靶向雌激素受体α (ER-α) 治疗乳腺癌的吲哚查尔酮衍生物的合成和计算机模拟研究

背景：乳腺癌是全球女性死亡的主要原因，且病例数日益增加。FDA 批准了许多治疗乳腺癌的药物。由于耐药性和选择性问题，需要开发更有效、副作用更少的药物。吲哚衍生物已显示出作为抗乳腺癌药物的显着药理学潜力。此外，掺入杂环支架的查耳酮衍生物在医学中发挥着重要作用。基于吲哚查尔酮的化合物具有改善生物活性和增强药物样特性的潜力。这促使我们探索合成针对雌激素受体α（ER-α）的吲哚查耳酮衍生物，以发现有效的抗乳腺癌药物。目的：合成吲哚查耳酮衍生物，并通过分子对接研究其与 ER-α 蛋白的结合相互作用，用于乳腺癌治疗。方法：在本研究中，使用常规加热合成了吲哚查尔酮衍生物。借助薛定谔软件，对化合物进行了分子相互作用以及 ADME（吸附、分布、代谢和排泄）研究。结果：在所有合成的化合物中，四种化合物（1、2、3和4）显示出更好的对接分数（分别为-10.24 kcal/mol、-10.15 kcal/mol、-9.40 kcal/mol、-9.29 kcal/mol） ）比标准他莫昔芬（-8.43 kcal/mol）高。结论：从计算机研究中，我们可以得出结论，合成系列中的四种化合物适合 ER-α 的活性位点。合成衍生物的 ADME 性能在可接受的范围内。未来，可以进一步探索这些化合物的生物活性。