Quayum Syeda Tasnim, Esha Nusrat Jahan Ikbal, Siraji Siam, Abbad Sanaa S Al, Alsunaidi Zainab H A, Almatarneh Mansour H, Rahman Shofiur, Alodhayb Abdullah N, Alibrahim Khuloud A, Kawsar Sarkar M A, Uddin Kabir M
Department of Biochemistry and Microbiology, North South University, Bashundhara, Dhaka 1217, Bangladesh.
Department of Chemistry, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
MethodsX. 2023 Dec 29;12:102537. doi: 10.1016/j.mex.2023.102537. eCollection 2024 Jun.
In exploring nature's potential in addressing liver-related conditions, this study investigates the therapeutic capabilities of flavonoids. Utilizing methodologies, we focus on flavone and its analogs (-) to assess their therapeutic potential in treating liver diseases. Molecular change calculations using density functional theory (DFT) were conducted on these compounds, accompanied by an evaluation of each analog's physiochemical and biochemical properties. The study further assesses these flavonoids' binding effectiveness and locations through molecular docking studies against six target proteins associated with human cancer. Tropoflavin and taxifolin served as reference drugs. The structurally modified flavone analogs (-) displayed a broad range of binding affinities, ranging from -7.0 to -9.4 kcal mol⁻¹, surpassing the reference drugs. Notably, flavonoid () exhibited significantly higher binding affinities with proteins Nrf2 (PDB:1 × 2 J) and DCK (PDB:1 × 2 J) (-9.4 and -8.1 kcal mol⁻¹) compared to tropoflavin (-9.3 and -8.0 kcal mol⁻¹) and taxifolin (-9.4 and -7.1 kcal mol⁻¹), respectively. Molecular dynamics (MD) simulations revealed that the docked complexes had a root mean square deviation (RMSD) value ranging from 0.05 to 0.2 nm and a root mean square fluctuation (RMSF) value between 0.35 and 1.3 nm during perturbation. The study concludes that 5,7-dihydroxyflavone () shows substantial promise as a potential therapeutic agent for liver-related conditions. However, further validation through and studies is necessary. Key insights from this study include:•Screening of flavanols and their derivatives to determine pharmacological and bioactive properties using ADMET, molinspiration, and pass prediction analysis.•Docking of shortlisted flavone derivatives with proteins having essential functions.•Analysis of the best protein-flavonoid docked complexes using molecular dynamics simulation to determine the flavonoid's efficiency and stability within a system.
在探索大自然在解决肝脏相关病症方面的潜力时，本研究调查了黄酮类化合物的治疗能力。利用相关方法，我们聚焦于黄酮及其类似物（-），以评估它们在治疗肝脏疾病方面的治疗潜力。对这些化合物进行了使用密度泛函理论（DFT）的分子变化计算，并对每个类似物的物理化学和生化性质进行了评估。该研究还通过针对与人类癌症相关的六种靶蛋白的分子对接研究，评估了这些黄酮类化合物的结合有效性和位置。曲黄酮和紫杉叶素用作参考药物。结构修饰的黄酮类似物（-）表现出广泛的结合亲和力，范围从-7.0至-9.4千卡摩尔⁻¹，超过了参考药物。值得注意的是，与曲黄酮（-9.3和-8.0千卡摩尔⁻¹）和紫杉叶素（-9.4和-7.1千卡摩尔⁻¹）相比，黄酮类化合物（）与蛋白质Nrf2（PDB:1×2J）和DCK（PDB:1×2J）表现出显著更高的结合亲和力（分别为-9.4和-8.1千卡摩尔⁻¹）。分子动力学（MD）模拟显示，对接复合物在扰动期间的均方根偏差（RMSD）值范围为0.05至0.2纳米，均方根波动（RMSF）值在0.35至1.3纳米之间。该研究得出结论，5,7-二羟基黄酮（）作为肝脏相关病症的潜在治疗剂显示出巨大的前景。然而，需要通过进一步的研究进行验证。本研究的关键见解包括：•使用ADMET、molinspiration和通过预测分析筛选黄烷醇及其衍生物，以确定其药理和生物活性特性。•将入围的黄酮衍生物与具有重要功能的蛋白质进行对接。•使用分子动力学模拟分析最佳的蛋白质-黄酮对接复合物，以确定黄酮类化合物在系统内的效率和稳定性。
