计算筛选尼日利亚药用植物中某些植物化学物质对镰状细胞病的作用。
Computational screening of phytochemicals present in some Nigerian medicinal plants against sickle cell disease.
机构信息
Department of Pure and Applied Chemistry, Osun State University, Osogbo, Nigeria.
Department of Chemistry and Industrial Chemistry, Bowen University, Iwo, Osun State, Nigeria.
出版信息
Sci Rep. 2024 Nov 1;14(1):26368. doi: 10.1038/s41598-024-75078-w.
Four hundred Phytochemical (bio-active) compounds having predictive activity for treating Sickle Cell Anemia were screened, using PASS online computational resource. Twenty-six compounds out of the four hundred compounds which showed high probability for treating sickle were further screened for pharmacokinetics profiles (ADMET properties) using SwissAdmet, AdmetSAR 2 and Pro-tox II online resources. Only thirteen compounds that displayed good ADMET properties from the twenty-six were further used for DFT calculations and molecular docking against carbonmonoxy sickle hemoglobin (PDB ID: 5E6E). Molecular docking analysis reinforced by DFT calculations showed that two compounds, phenanthrene-5,6-dione (A9) and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxychromen-4-one (A13, Luteolin) had the best binding affinity of - 8.3 and - 8.9 kcal/mol, respectively, compared to voxelotor (GBT-440), a drug use in treating sickle cell disease. Molecular dynamic simulations showed that 2-(3,4-dihydroxyphenyl)-5,7-dihydroxychromen-4-one (A13, Luteolin) is highly stable with the protein than voxelotor.
使用 PASS 在线计算资源筛选出具有治疗镰状细胞贫血预测活性的 400 种植物化学（生物活性）化合物。从这 400 种化合物中筛选出 26 种对治疗镰状有高概率的化合物，使用 SwissAdmet、AdmetSAR 2 和 Pro-tox II 在线资源进一步筛选药代动力学特征（ADMET 属性）。在这 26 种化合物中，只有 13 种显示出良好的 ADMET 特性的化合物被进一步用于 DFT 计算和针对碳氧合镰状血红蛋白（PDB ID：5E6E）的分子对接。DFT 计算强化的分子对接分析表明，两种化合物，菲醌-5,6-二酮（A9）和 2-（3,4-二羟基苯基）-5,7-二羟基色原酮-4-酮（A13，木犀草素）的结合亲和力最好，分别为-8.3 和-8.9 kcal/mol，而与用于治疗镰状细胞病的药物 voxeltor（GBT-440）相比。分子动力学模拟表明，2-（3,4-二羟基苯基）-5,7-二羟基色原酮-4-酮（A13，木犀草素）与蛋白的稳定性远高于 voxeltor。
Zotero 插件