The International Centre for Interdisciplinary Solutions on Antibiotics and Secondary Metabolites, Republican Collection of Microorganisms, Nur-Sultan 010000, Kazakhstan.
The Laboratory of Engineering Profile of NMR Spectroscopy, Sh. Ualikhanov Kokshetau University, Kokshetau 020000, Kazakhstan.
Molecules. 2022 Mar 31;27(7):2281. doi: 10.3390/molecules27072281.
A new dicoumarin, jusan coumarin, (), has been isolated from aerial parts. The chemical structure of jusan coumarin was estimated, by 1D, 2D NMR as well as HR-Ms spectroscopic methods, to be 7-hydroxy-6-methoxy-3-[(2-oxo-2H-chromen-6-yl)oxy]-2H-chromen-2-one. As the first time to be introduced in nature, its potential against SARS-CoV-2 has been estimated using various in silico methods. Molecular similarity and fingerprints experiments have been utilized for against nine co-crystallized ligands of COVID-19 vital proteins. The results declared a great similarity between Jusan Coumarin and , the ligand of COVID-19 main protease (PDB ID: 6W63), M. To authenticate the obtained outputs, a DFT experiment was achieved to confirm the similarity of and . Consequently, was docked against M. The results clarified that bonded in a correct way inside M active site, with a binding energy of -18.45 kcal/mol. Furthermore, the ADMET and toxicity profiles of were evaluated and showed the safety of and its likeness to be a drug. Finally, to confirm the binding and understand the thermodynamic characters between and M, several molecular dynamics (MD) simulations studies have been administered. Additionally, the known coumarin derivative, 7-isopentenyloxycoumarin (), has been isolated as well as β-sitosterol ().
从该植物的地上部分分离得到一种新的二香豆素，即芫花素（）。芫花素的化学结构通过 1D、2D NMR 以及高分辨质谱（HR-MS）等光谱方法进行了推测，其结构为 7-羟基-6-甲氧基-3-[(2-氧代-2H-色烯-6-基)氧基]-2H-色烯-2-酮。由于它是首次在自然界中被发现，因此利用多种计算方法对其抗 SARS-CoV-2 的潜力进行了评估。利用分子相似性和指纹实验对其与 9 种与 COVID-19 关键蛋白共结晶的配体进行了对抗研究。结果表明，芫花素与 COVID-19 主蛋白酶（PDB ID：6W63）的配体 之间具有很大的相似性。为了验证获得的结果，进行了 DFT 实验以确认 与 的相似性。因此，对 进行了对接实验。结果表明，在 M 的活性部位，以 -18.45 kcal/mol 的结合能正确地结合了 。此外，还对 进行了 ADMET 和毒性预测，结果表明 具有安全性，并且与 具有相似性，可能成为一种药物。最后，为了确认 与 M 之间的结合以及理解它们之间的热力学特性，进行了几项分子动力学（MD）模拟研究。此外，还分离到了已知的香豆素衍生物，7-异戊烯氧基香豆素（），以及 β-谷甾醇（）。
