El Bakri Youness, Mohamed Shaaban K, Saravanan Kandasamy, Ahmad Sajjad, Mahmoud Ahmed A, Abdel-Raheem Shaban A A, El-Sayed Wael M, Mague Joel T, Goumri Said Souraya
Department of Theoretical and Applied Chemistry, South Ural State University, Chelyabinsk, Russian Federation.
Chemistry and Environmental Division, Manchester Metropolitan University, Manchester M1 5GD, England, United Kingdom.
J King Saud Univ Sci. 2023 Jun;35(4):102628. doi: 10.1016/j.jksus.2023.102628. Epub 2023 Mar 4.
In the present work, we describe the extraction of a natural product namely 1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1)-one, and its structure was confirmed by single crystal X-ray diffraction analysis. The conformations of the 5-, 6-, and 7-membered rings in the title compound, CHO, have been probed by a Cremer-Pople puckering analysis. C-H···O hydrogen bonds generate chains in the crystal that stretch along the -axis direction. The Hirshfeld surface analysis method was used to stabilize the crystal packing of the natural compound. Accompanied by experimental studies, quantum chemical calculations were also performed to compare the structural elucidation and the results of these geometrical parameters exhibited excellent agreement. The compound was also docked with several drug targets of the SARS-CoV-2 virus and found to show the best binding with the main protease enzyme, having a binding energy of -12.31 kcal/mol and interacting with His41 and Cys145 residues. The dynamic stability deciphered the complex to be stable with an average RMSD of 3.8 Å. The compound dynamics with the enzyme showed the compound conformation to be highly stable. The intermolecular binding free energy determined the compound-main protease enzyme to show high interaction energy of < 40 kcal/mol. Together, these studies demonstrate the compound to be a lead structure against SARS-CoV-2.
在本工作中，我们描述了一种天然产物即1,4,9,9-四甲基八氢-4,7-(环氧亚甲基)薁-5(1)-酮的提取，并通过单晶X射线衍射分析确定了其结构。通过Cremer-Pople褶皱分析研究了标题化合物CHO中5元、6元和7元环的构象。C-H···O氢键在晶体中形成沿z轴方向延伸的链。采用Hirshfeld表面分析方法来稳定天然化合物的晶体堆积。在实验研究的同时，还进行了量子化学计算，以比较结构解析，这些几何参数的结果显示出极好的一致性。该化合物还与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒的几个药物靶点进行对接，发现与主要蛋白酶具有最佳结合，结合能为-12.31 kcal/mol，并与His41和Cys145残基相互作用。动力学稳定性表明该复合物稳定，平均均方根偏差（RMSD）为3.8 Å。该化合物与酶的动力学表明化合物构象高度稳定。分子间结合自由能确定该化合物与主要蛋白酶显示出小于40 kcal/mol的高相互作用能。总之，这些研究表明该化合物是针对SARS-CoV-2的先导结构。
