Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece.
Laboratory of Polymer Chemistry, Department of Chemistry, National and Kapodistrian Nikitas Georgiou University of Athens, Panepistimioupolis Zografou, 11571 Athens, Greece.
Molecules. 2022 Apr 14;27(8):2537. doi: 10.3390/molecules27082537.
The structure assignment and conformational analysis of thiosemicarbazone and thiocarbohydrazone were performed through homonuclear and heteronuclear 2D Nuclear Magnetic Resonance (NMR) spectroscopy (2D-COSY, 2D-NOESY, 2D-HSQC, and 2D-HMBC) and quantum mechanics (QM) calculations using Functional Density Theory (DFT). After the structure identification of the compounds, various conformations of the two compounds were calculated using DFT. The two molecules showed the most energy-favorable values when their two double bonds adopted the configuration. These configurations were compatible with the spatial correlations observed in the 2D-NOESY spectrum. In addition, due to the various isomers that occurred, the energy of the transition states from one isomer to another was calculated. Finally, molecular binding experiments were performed to detect potential targets for and derived from SwissAdme. In silico molecular binding experiments showed favorable binding energy values for all four enzymes studied. The strongest binding energy was observed in the enzyme butyrylcholinesterase. ADMET calculations using the preADMET and pKCSm software showed that the two molecules appear as possible drug leads.
通过同核和异核二维核磁共振波谱（2D-COSY、2D-NOESY、2D-HSQC 和 2D-HMBC）以及使用功能密度理论（DFT）的量子力学（QM）计算，对硫代半卡巴腙和硫代碳酰肼的结构进行了归属和构象分析。在确定化合物的结构后，使用 DFT 计算了两种化合物的各种构象。当两个双键采用 构象时，两个分子表现出最有利的能量值。这些构象与在 2D-NOESY 光谱中观察到的空间相关性一致。此外，由于存在各种异构体，计算了从一种异构体到另一种异构体的过渡态的能量。最后，进行了分子结合实验，以检测源自 SwissAdme 的 和 可能的靶标。计算机分子结合实验显示，对于所研究的所有四种酶，都具有有利的结合能值。在丁酰胆碱酯酶中观察到最强的结合能。使用 preADMET 和 pKCSm 软件进行 ADMET 计算表明，这两个分子可能成为潜在的药物先导化合物。
