Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, 61441, Kingdom of Saudi Arabia.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Al-Quwayiyah, Shaqra University, Riyadh, 15526, Kingdom of Saudi Arabia.
Med Oncol. 2023 Jul 2;40(8):218. doi: 10.1007/s12032-023-02094-7.
Cervical cancer is a significant cause of morbidity and mortality in women worldwide. Despite the availability of effective therapies, the development of drug resistance and adverse side effects remain significant challenges in cervical cancer treatment. Thus, repurposing existing drugs as multitargeted therapies for cervical cancer is an attractive approach. In this study, we extensively screened the complete prepared FDA-approved drugs and identified the repurposing potential of taxifolin, a flavonoid with known antioxidant and anti-inflammatory properties, as a multitargeted therapy for cervical cancer. We performed a computational analysis using molecular docking with various sampling algorithms, namely HTVS, SP, and XP algorithms, for robust sampling pose and filtered with MM/GBSA analysis to determine the binding affinity of taxifolin with potential targets involved in cervical cancer, such as Symmetric Mad2 Dimer, replication initiation factor MCM10-ID, TPX2, DNA polymerase epsilon B-subunit, human TBK1, and alpha-v beta-8. We then conducted MD simulations to investigate the stability and conformational changes of the complex formed between taxifolin and the mentioned proteins. Our results suggest that taxifolin has a high binding affinity ranging from - 6.094 to - 9.558 kcal/mol, indicating its potential as a multitargeted therapy for cervical cancer. Furthermore, interaction fingerprints, pharmacokinetics and MD simulations revealed that the Taxifolin-target complexes remained stable over the simulation period, indicating that taxifolin may bind to the targets for an extended period. Our study suggests that taxifolin has the potential as a multitargeted therapy for cervical cancer, and further experimental studies are necessary to validate our findings.
宫颈癌是全球女性发病率和死亡率的重要原因。尽管有有效的治疗方法，但耐药性的发展和不良反应仍然是宫颈癌治疗的重大挑战。因此，将现有药物重新用于宫颈癌的多靶点治疗是一种有吸引力的方法。在这项研究中，我们广泛筛选了完整的已批准的 FDA 药物，并确定了具有已知抗氧化和抗炎特性的类黄酮紫杉素作为宫颈癌多靶点治疗的再利用潜力。我们使用各种采样算法（即 HTVS、SP 和 XP 算法）进行分子对接计算分析，以进行稳健的采样姿势，并通过 MM/GBSA 分析进行过滤，以确定紫杉素与宫颈癌相关的潜在靶标的结合亲和力，例如对称 Mad2 二聚体、复制起始因子 MCM10-ID、TPX2、DNA 聚合酶 epsilon B 亚基、人 TBK1 和 alpha-v beta-8。然后，我们进行 MD 模拟，以研究紫杉素与所述蛋白形成的复合物的稳定性和构象变化。我们的结果表明，紫杉素具有从-6.094 到-9.558 kcal/mol 的高结合亲和力，表明其作为宫颈癌多靶点治疗的潜力。此外，相互作用指纹、药代动力学和 MD 模拟表明，紫杉素-靶复合物在模拟期间保持稳定，表明紫杉素可能在较长时间内与靶结合。我们的研究表明，紫杉素具有作为宫颈癌多靶点治疗的潜力，需要进一步的实验研究来验证我们的发现。
