Rajesh Kumar T, Premkumar R, Langeswaran K, Ramavenkateswari K, Anitha S, Sangavi P, Sangeetha R
Department of Physics, G.T.N. Arts College, Dindigul, Tamil Nadu, India.
Department of Physics, N.M.S.S.V.N. College, Nagamalai, Madurai, Tamil Nadu, India.
J Biomol Struct Dyn. 2023;41(23):13595-13604. doi: 10.1080/07391102.2023.2192795. Epub 2023 Apr 3.
HDAC protein is associated with hepatocellular carcinoma. Different medicinal plants were selected for this study to analyze the inhibitory efficacy against the target protein, HDAC. Using virtual screening, we filtered out the best compounds, and molecular docking (XP) was carried out for the top compounds which filtered out. The molecular docking results showed that the title compound (2-methoxy-4-prop-2-enylphenyl) N-(2-methoxy-4-nitrophenyl) carbamate (MEMNC) has the highest docking score of about -7.7 kcal/mol against the targeted protein histone deacetylase (HDAC) compared with the other selected phytocompounds. From the molecular dynamics analysis, the RMSD and RMSF plots depicted the overall stability of the protein-ligand complex. Toxicity properties show the acceptable range of various kinds of toxicity that were predicted using the ProTox-II server. In addition, DFT quantum chemical and physicochemical properties of the MEMNC molecule were reported. Initially, the molecular structure of the MEMNC molecule was optimized and harmonic vibrational frequencies were calculated using DFT/B3LYP method with a cc-pVTZ basis set using Gaussian 09 program. The calculated vibrational wavenumber values were assigned based on Potential Energy Distribution calculations using the VEDA 4.0 program and correlated well with the previous literature values. The molecule has bioactivity as a result of intramolecular charge transfer interactions, as demonstrated by frontier molecular orbital analysis. Molecular electrostatic potential surface and Mulliken atomic charge distribution analyses validate the reactive sites of the molecule. Thus, the title compound can be used as a potential inhibitor of HDAC protein, which paves the way for designing novel drugs to treat Hepatocellular carcinoma.Communicated by Ramaswamy H. Sarma.
组蛋白去乙酰化酶（HDAC）蛋白与肝细胞癌相关。本研究选取了不同的药用植物来分析其对靶蛋白HDAC的抑制效果。通过虚拟筛选，我们筛选出了最佳化合物，并对筛选出的顶级化合物进行了分子对接（XP）。分子对接结果表明，与其他选定的植物化合物相比，标题化合物（2-甲氧基-4-丙烯基苯基）N-（2-甲氧基-4-硝基苯基）氨基甲酸酯（MEMNC）与靶蛋白组蛋白去乙酰化酶（HDAC）的对接得分最高，约为-7.7 kcal/mol。从分子动力学分析来看，均方根偏差（RMSD）和均方根波动（RMSF）图描绘了蛋白质-配体复合物的整体稳定性。毒性特性显示了使用ProTox-II服务器预测的各种毒性的可接受范围。此外，还报道了MEMNC分子的密度泛函理论（DFT）量子化学和物理化学性质。最初，使用高斯09程序，采用cc-pVTZ基组，通过DFT/B3LYP方法对MEMNC分子的结构进行了优化，并计算了其简正振动频率。使用VEDA 4.0程序基于势能分布计算对计算得到的振动波数值进行了归属，且与先前的文献值相关性良好。前沿分子轨道分析表明，该分子由于分子内电荷转移相互作用而具有生物活性。分子静电势表面和穆利肯原子电荷分布分析验证了该分子的反应位点。因此，标题化合物可作为HDAC蛋白的潜在抑制剂，为设计治疗肝细胞癌的新型药物铺平了道路。由拉马斯瓦米·H·萨尔马通讯。
