Department of Pure and Applied Chemistry, Osun State University, Osogbo, Nigeria.
Department of Chemistry and Industrial Chemistry, Bowen University, Iwo, Osun State, Nigeria.
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。
