Structure Based Multitargeted Molecular Docking Analysis of Selected Furanocoumarins against Breast Cancer
Structure Based Multitargeted Molecular Docking Analysis of Selected Furanocoumarins against Breast Cancer
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DOI：
10.1038/s41598-019-52162-0
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发表时间：
2019-10-31
影响因子：
4.6
通讯作者：
Pattanayak, Shakti P. Rasad
中科院分区：
文献类型：
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作者：
Acharya, Reetuparna;Chacko, Shinu;Pattanayak, Shakti P. Rasad
乳腺癌是全球面临的最大难题之一，目前的治疗方法是通过使用部分激动剂/拮抗剂靶向激素受体。治疗乳腺癌的有效药物有他莫昔芬、曲妥珠单抗、紫杉醇等，这些药物在患者中显示出不良反应和耐药性。该研究的目的是研究对ER α、PR、EGFR和mTOR抑制具有强效作用的某些植物化学物质。由于蛋白质-配体相互作用在药物设计中起着至关重要的作用，因此目前的研究是通过使用分子对接来进行的。ER α、PR、EGFR和mTOR的3D结构从蛋白质数据库获得，并使用FlexX与呋喃香豆素化合物的23个3D PubChem结构对接。通过对呋喃香豆素应用Lipinski's rule of five来检查药物相似性以评价抗乳腺癌活性。使用适当的体外技术分别进行ER α、EGFR和mTOR的拮抗剂和抑制测定。结果证实，花椒毒酚对乳腺癌具有最好的对接评分，其次是Bergapten、Angelicin、Pesticen和Isoimperatorin。此外，体外结果也验证了分子对接分析。这项研究表明，选定的呋喃香豆素类药物可以进一步研究和评估乳腺癌的治疗和管理策略。
Breast cancer is one of the biggest global dilemmas and its current therapy is to target the hormone receptors by the use of partial agonists/antagonists. Potent drugs for breast cancer treatment are Tamoxifen, Trastuzumab, Paclitaxel, etc. which show adverse effects and resistance in patients. The aim of the study has been on certain phytochemicals which has potent actions on ER alpha, PR, EGFR and mTOR inhibition. The current study is performed by the use of molecular docking as protein-ligand interactions play a vital role in drug design. The 3D structures of ER alpha, PR, EGFR and mTOR were obtained from the protein data bank and docked with 23 3D PubChem structures of furanocoumarin compounds using FlexX. Drug-likeness property was checked by applying the Lipinski's rule of five on the furanocoumarins to evaluate anti-breast cancer activity. Antagonist and inhibition assay of ERa, EGFR and mTOR respectively has been performed using appropriate in-vitro techniques. The results confirm that Xanthotoxol has the best docking score for breast cancer followed by Bergapten, Angelicin, Psoralen and Isoimperatorin. Further, the in-vitro results also validate the molecular docking analysis. This study suggests that the selected furanocoumarins can be further investigated and evaluated for breast cancer treatment and management strategies.