Tarbeeva Darya V, Krylova Natalya V, Iunikhina Olga V, Likhatskaya Galina N, Kalinovskiy Anatoliy I, Grigorchuk Valeria P, Shchelkanov Mikhail Yu, Fedoreyev Sergey A
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, Russia.
G.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, 690087 Vladivostok, Russia.
Fitoterapia. 2022 Mar;157:105121. doi: 10.1016/j.fitote.2021.105121. Epub 2022 Jan 3.
We investigated the ability of six prenylated prerocarpans, stilbenoid, and a new dimeric flavonoid, lespebicolin B, from stem bark as well as two 3-O-rutinosides and a mixture of 3-O-β-D-glucosides of quercetin and kaempferol from flowers of Lespedeza bicolor to inhibit HSV-1 replication in Vero cells. Pretreatment of HSV-1 with polyphenolic compounds (direct virucidal effect) showed that pterocarpans lespedezol A (1), (6aR,11aR)-6a,11a-dihydrolespedezol A (2), (6aR,11aR)-2-isoprenyldihydrolespedezol A (4), and (6aR,11aR,3'R)-dihydrolespedezol A (5) significantly inhibited viral replication, with a selective index (SI) ≥10. Compound 4 possessed the lowest 50% - inhibiting concentration (IC) and the highest SI values (2.6 μM and 27.9, respectively) in this test. (6aR,11aR)-2-Isoprenyldihydrolespedezol A (4) also had a moderate effect under simultaneous treatment of Vero cells with the tested compound and virus (IC and SI values were 5.86 μM and 12.4, respectively). 3-O-rutinosides of quercetin and kaempferol and a mixture of 3-O-β-D-glucosides of quercetin and kaempferol (10 and 12) also showed significant virucidal activity, with SI values of 12.5, 14.6, and 98.2, respectively, and IC values of 8.6, 12.2, and 3.6, respectively. We also performed a quantitative structure-activity relationship (QSAR) analysis of data on the virucidal activity of polyphenolics with 4 < pIC < 6. It was found that the virucidal activity of these compounds depended on both the structure of the aromatic part and the conformation of geranyl and isoprenyl side chains of their molecules. These findings are correlated with the largest value of the principal moment of inertia (pmi) descriptor describing the geometry of molecules.
我们研究了来自二色胡枝子茎皮的六种异戊烯基前紫檀素、二苯乙烯类化合物以及一种新的二聚体黄酮类化合物——胡枝子黄素B，以及来自二色胡枝花的两种3 - O - 芸香糖苷和槲皮素与山奈酚的3 - O - β - D - 葡萄糖苷混合物对Vero细胞中单纯疱疹病毒1型（HSV - 1）复制的抑制能力。用多酚类化合物对HSV - 1进行预处理（直接杀病毒作用）表明，紫檀素类化合物胡枝子醇A（1）、（6aR，11aR）- 6a，11a - 二氢胡枝子醇A（2）、（6aR，11aR）- 2 - 异戊烯基二氢胡枝子醇A（4）和（6aR，11aR，3'R）- 二氢胡枝子醇A（5）显著抑制病毒复制，选择性指数（SI）≥10。在该试验中，化合物4的50%抑制浓度（IC）最低，SI值最高（分别为2.6 μM和27.9）。（6aR，11aR）- 2 - 异戊烯基二氢胡枝子醇A（4）在将受试化合物与病毒同时处理Vero细胞时也有中等效果（IC和SI值分别为5.86 μM和12.4）。槲皮素和山奈酚的3 - O - 芸香糖苷以及槲皮素和山奈酚的3 - O - β - D - 葡萄糖苷混合物（10和12）也显示出显著的杀病毒活性，SI值分别为12.5、14.6和98.2，IC值分别为8.6、12.2和3.6。我们还对4 < pIC < 6的多酚类化合物杀病毒活性数据进行了定量构效关系（QSAR）分析。发现这些化合物的杀病毒活性既取决于芳香部分的结构，也取决于其分子中香叶基和异戊烯基侧链的构象。这些发现与描述分子几何形状的主惯性矩（pmi）描述符的最大值相关。
