乳腺癌是妇女致死性癌症的第二大原因，也是最常见的恶性肿瘤。由于大多数化疗药物易于复发、耐药和副作用等问题，科学家们开始转向有益的预防和治疗制剂，如天然分子。3-葡萄糖苷化的槲皮素是一种天然黄酮醇苷，已知具有多种药理活性，但有关其抗增殖能力的报道较少。本研究旨在利用细胞毒性实验、体外和体内试验方法，通过计算机辅助和分子动力学分析，调查3-葡萄糖苷化的槲皮素在乳腺癌细胞系中的抗增殖效果及其对透明质酸酶（HYAL）和鸟氨酸脱羧酶（ODC）两个乳腺癌预后标志物的调节潜力。3-葡萄糖苷化的槲皮素显著抑制MDA-MB-231细胞的生长，在SRB（IC50为88.64±7.14μM）和MTT（56.26±8.50μM）试验中显示出较低的细胞毒性。它通过诱导细胞在G0/G1期停滞来抑制细胞向S期的转变，并且抑制率为1.10倍。它与ODC（-7.90 kcal/mol）和HYAL（-9.46 kcal/mol）有强大的结合作用，并抑制了ODC（15.22±2.61μM）和HYAL（11.92±2.89μM）的活性，但在体内实验中，主要对HYAL（21.46±4.03μM）产生了显著的反应。此外，它还表现出1.38倍下调HYAL的能力，并与HYAL形成稳定的复合物。3-葡萄糖苷化的槲皮素的结合口袋与模拟过程中的口袋完全一致，表明其积极阻断了透明质酸酶。计算预测表明该物质具有安全性。这些观察结果提示，3-葡萄糖苷化的槲皮素可作为设计和合成管理非激素依赖性乳腺癌的新型安全药物的药效团。由Ramaswamy H. Sarma提供的信息。

Breast cancer is the second-leading cause of cancer-related death in women and the most often diagnosed malignancy. As the majority of chemotherapeutic medications are associated with recurrence, drug resistance, and side effects, scientists are shifting to beneficial agents for prevention and treatment, such as natural molecules. Myricetin 3-rhamnoside, a natural flavonol glycoside is known for diverse pharmacological activities but fewer reports describe the antiproliferative ability. The study aims to investigate the antiproliferative efficacy and target [hyaluronidase (HYAL) and ornithine decarboxylase (ODC), two poor breast cancer prognostic markers] modulatory potential of myricetin 3-rhamnoside on breast cancer cell lines using cytotoxicity assays and in silico docking, molecular dynamics analysis, cell-free and cell-based test methods. Myricetin 3-rhamnoside significantly retard the growth of MDA-MB-231 cells in SRB (IC50 88.64 ± 7.14 µM) and MTT (56.26 ± 8.50 µM) assay. It suppressed the transition of cells to the S-phase by inducing arrest in the G0/G1 phase with a fold change of 1.10. It shows robust binding interaction with ODC (-7.90 kcal/mol) and HYAL (-9.46 kcal/mol) and inhibits ODC (15.22 ± 2.61 µM) and HYAL (11.92 ± 2.89 µM) activity, but in a cell-based assay, the prominent response was observed against HYAL (21.46 ± 4.03 µM). Besides, it shows a 1.38 fold-down regulation of HYAL and forms a stable complex with HYAL. The binding pocket for myricetin 3-rhamnoside and the simulation pocket during the simulation are identical, indicating that myricetin 3-rhamnoside is actively blocking hyaluronidase. The computational prediction suggests it is a safe molecule. These observations imply that myricetin 3-rhamnoside could be used as a pharmacophore to design and synthesize a novel and safe agent for managing hormone-independent breast cancer.Communicated by Ramaswamy H. Sarma.