Spirostanol Sapogenins and Saponins from L. Structural Characterization by 2D NMR, Theoretical GIAO DFT Calculations and Molecular Modeling.

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.