Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
Molecules. 2021 May 18;26(10):2999. doi: 10.3390/molecules26102999.
Two new spirostanol sapogenins (5β-spirost-25(27)-en-1β,2β,3β,5β-tetrol and its 25,27-dihydro derivative, (25S)-spirostan-1β,2β,3β,5β-tetrol ) and four new saponins were isolated from the roots and rhizomes of L. together with known sapogenins (isolated from ): 5β-spirost-25(27)-en-1β,3β-diol , (25S)-spirostan-1β,3β-diol , 5β-spirost-25(27)-en-1β,3β,4β,5β-tetrol , (25S)-spirostan-1β,3β,4β,5β-tetrol , 5β-spirost-25(27)-en-1β,2β,3β,4β,5β-pentol and (25S)-spirostan-1β,2β,3β,4β,5β-pentol . New steroidal saponins were found to be pentahydroxy 5--glycosides; 5β-spirost-25(27)-en-1β,2β,3β,4β,5β-pentol 5--β-galactopyranoside , 5β-spirost-25(27)-en-1β,2β,3β,4β,5β-pentol 5--β-arabinonoside , 5β-(25S)-spirostan-1β,2β,3β,4β,5β-pentol 5--galactoside and 5β-(25S)-spirostan-1β,2β,3β,4β,5β-pentol 5--arabinoside were isolated for the first time. The structures of those compounds were determined by NMR spectroscopy, including 2D COSY, HMBC, HSQC, NOESY, ROESY experiments, theoretical calculations of shielding constants by GIAO DFT, and mass spectrometry (FAB/LSI HR MS). An attempt was made to test biological activity, particularly as potential chemotherapeutic agents, using in silico methods. A set of 12 compounds was docked to the PDB structures of HER2 receptor and tubulin. The results indicated that diols have a higher affinity to the analyzed targets than tetrols and pentols. Two compounds (25S)-spirosten-1β,3β-diol and 5β-spirost-25(27)-en-1β,2β,3β,4β,5β-pentol 5--galactoside were selected for further evaluation of biological activity.
从 L. 的根和根茎中分离得到两种新的螺甾烷醇皂甙元（5β-螺甾-25(27)-烯-1β，2β，3β，5β-四醇及其 25，27-二氢衍生物（25S）-螺甾-1β，2β，3β，5β-四醇）和四种新的皂甙，以及已知的皂甙元（从 中分离得到）：5β-螺甾-25(27)-烯-1β，3β-二醇，（25S）-螺甾-1β，3β-二醇，5β-螺甾-25(27)-烯-1β，3β，4β，5β-四醇，（25S）-螺甾-1β，3β，4β，5β-四醇，5β-螺甾-25(27)-烯-1β，2β，3β，4β，5β-五醇和（25S）-螺甾-1β，2β，3β，4β，5β-五醇。新的甾体皂甙被发现为五羟基 5--糖苷；5β-螺甾-25(27)-烯-1β，2β，3β，4β，5β-五醇 5--β-半乳糖吡喃糖苷，5β-螺甾-25(27)-烯-1β，2β，3β，4β，5β-五醇 5--β-阿拉伯糖苷，5β-（25S）-螺甾-1β，2β，3β，4β，5β-五醇 5--半乳糖苷和 5β-（25S）-螺甾-1β，2β，3β，4β，5β-五醇 5--阿拉伯糖苷首次分离得到。通过 NMR 光谱，包括 2D COSY、HMBC、HSQC、NOESY、ROESY 实验、GIAO DFT 理论计算屏蔽常数和质谱（FAB/LSI HR MS），确定了这些化合物的结构。尝试使用计算方法测试生物活性，特别是作为潜在的化疗药物。一组 12 种化合物被对接至 HER2 受体和微管蛋白的 PDB 结构。结果表明，二醇对分析靶标具有更高的亲和力，而四醇和五醇则没有。两种化合物（25S）-螺甾烯-1β，3β-二醇和 5β-螺甾-25(27)-烯-1β，2β，3β，4β，5β-五醇 5--半乳糖苷被选为进一步评估生物活性的候选化合物。
