PDF(Pubmed)
Abstract：
Wnt/β-catenin signaling pathway plays a role in cancer development, organogenesis, and embryogenesis. The abnormal activation promotes cancer stem cell renewal, proliferation, and differentiation. In the present study, molecular docking simulation and ADMET studies were carried out on selected bioactive compounds in search of β-catenin protein inhibitors for drug discovery against cancer. Blind docking simulation was performed using PyRx software on Autodock Vina. β-catenin protein (PDB ID: 1jdh) and 313 bioactive compounds (from PubChem database) with selected standard anticancer drugs were used for molecular docking. The ADMET properties of the best-performing compounds were calculated using SwissADME and pkCMS web servers. The results obtained from the molecular docking study showed that glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside-1, diosmin, and rutin had the best binding interactions with β-catenin protein based on their binding affinities. Glycyrrhizic acid and solanine had the same and lowest binding energy of -8.5 kcal/mol. This was followed by polyphyllin I with -8.4 kcal/mol, and crocin, hypericin, and tubeimoside-1 which all had a binding energy of 8.1 kcal/mol. Other top-performing compounds include diosmin and rutin with binding energy of -8.0 kcal/mol. The ADMET study revealed that the following compounds glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside-1, diosmin, rutin, and baicalin all violated Lipinski\'s rule of 5 which implies poor oral bioavailability. However, based on the binding energy score, it was suggested that these pharmacologically active compounds are potential molecules to be tested against cancer.
摘要：
Wnt/β-catenin信号通路在肿瘤的发生发展中发挥着重要作用,器官发生，和胚胎发生。异常激活促进癌症干细胞的更新，扩散,和差异化。在本研究中,分子对接模拟和ADMET研究进行了选择的生物活性化合物，以寻找β-catenin蛋白抑制剂，用于发现抗癌药物。在AutodockVina上使用PyRx软件进行盲对接仿真。β-连环蛋白蛋白(PDBID:1jdh)和313种生物活性化合物(来自PubChem数据库)与选定的标准抗癌药物用于分子对接。使用SwissADME和pkCMS网络服务器计算性能最佳的化合物的ADMET特性。分子对接研究结果表明,甘草酸,茄碱,PolyphylinI,crocin,金丝桃素,土贝莫苷-1，地奥司明，根据它们的结合亲和力，芦丁与β-catenin蛋白具有最佳的结合相互作用。甘草酸和茄碱具有相同且最低的结合能-8.5kcal/mol。其次是-8.4kcal/mol的多叶黄素I，和Crocin,金丝桃素,和tubeimoside-1，它们的结合能均为8.1kcal/mol。其他表现最好的化合物包括具有-8.0kcal/mol的结合能的地奥司明和芦丁。ADMET研究表明，以下化合物甘草酸，茄碱,PolyphylinI,crocin,金丝桃素,土贝莫苷-1，地奥司明，芦丁,和黄芩苷都违反了Lipinski的5法则，这意味着口服生物利用度差。然而,根据结合能得分，有人认为，这些药理活性化合物是潜在的抗癌分子。
