乳腺癌(BC)是仅次于肺癌的第二大癌症原因。这种疾病影响了数百万人,并导致许多人死亡。在乳腺癌细胞的转移中,拓扑异构酶IIα起着至关重要的作用。因此,这项研究旨在通过在早期抑制该酶来鉴定针对BC的潜在类黄酮化合物。根据以前的研究,我们使用PyRx0.8和Schrodinger应用程序选择并筛选了几种具有潜在抗乳腺癌活性的植物来源的类黄酮化合物,以进行初步的分子对接:杨梅素(-11.6kcal/mol)和槲皮素(-10.0kcal/mol)的最高对接得分。接下来,我们评估了Way2Drug服务器上的前四种化合物,以完成细胞毒性评估,在各种细胞系中表现出抗癌和抗乳腺癌活性。根据药代动力学研究,4种化合物表现出优异的价值,其功能与药物样分子相似.此外,杨梅素,槲皮素,莫林展示了最多的氢键,与相应的受体形成残基asn120,thr147和lys168。使用Desmond模拟器验证了蛋白质-配体复合物,并将他们的数据与抗乳腺癌药物阿霉素进行比较。在仿真分析中,对各种参数进行了评估,包括RMSD,RMSF,Rg,SASA,MolSA,PSA,和氢键相互作用。最后,用MM-GBSA操作验证了我们的动态仿真结果,和杨梅素和槲皮素有最大的分数-72.74344651,-66.66771823千卡/摩尔,比对照药物出色。因此,计算研究方法确定了杨梅素,槲皮素,在动物和细胞系研究的进一步证实后,Morin可以在工业上开发用于乳腺癌的替代治疗。
Breast cancer (BC) is the second-leading cause of cancer after lung cancer. The disease has affected millions of people and resulted in many deaths. In the metastasis of breast cancer cells, Topoisomerase IIα plays a vital role. Therefore, this investigation aims to identify potential flavonoid compounds against BC by inhibiting this enzyme at an early stage. Based on previous studies, we selected and screened several plant-derived flavonoid compounds with potential anti-breast cancer activity using PyRx 0.8 and Schrodinger applications for preliminary molecular docking: the highest docking scores of
Myricetin (-11.6 kcal/mol) and Quercetin (-10.0 kcal/mol). Next, we evaluated the top four compounds on the Way2Drug server to complete the cytotoxicity evaluation, which demonstrated anti-cancer and anti-breast cancer activity in various cell lines. According to pharmacokinetics studies, four compounds exhibited outstanding values and functioned similar to drug-like molecules. Moreover,
Myricetin, Quercetin, and Morin displayed the highest number of hydrogen bonds, with the corresponding receptor forming residues asn120, thr147, and lys168. The protein-ligand complexes were validated using the Desmond simulator, and their data were compared to the anti-breast cancer drug Doxorubicin. In the simulation analysis, various parameters were evaluated, including RMSD, RMSF, Rg, SASA, MolSA, PSA, and hydrogen bond interaction. Finally, validated our dynamic simulation result with MM-GBSA operation, and
Myricetin and Quercetin had the greatest score of -72.74344651, -66.66771823 kcal/mol, which is outstanding than the control drug. Hence, the computational research approach determined that
Myricetin, Quercetin, and Morin could be industrially developed for the alternative treatment of breast cancer following additional confirmation from animal and cell line studies.