Glechomanamides A–C, Germacrane Sesquiterpenoids with an Unusual Δ8-7,12-Lactam Moiety from Salvia scapiformis and Their Antiangiogenic Activity
| Autor: | Sang Kook Lee, Ri Zhen Huang, Yan Kui Zhu, Heng-Shan Wang, Dong Liang, Cai Yi Wang, Dong-Chan Oh, Donghwa Kim |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Pharmacology
Tube formation 010405 organic chemistry Stereochemistry Angiogenesis Chemical structure Organic Chemistry Pharmaceutical Science 01 natural sciences 0104 chemical sciences Analytical Chemistry 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Complementary and alternative medicine chemistry Drug Discovery Lactam Molecular Medicine Moiety Hemiacetal Lead compound Two-dimensional nuclear magnetic resonance spectroscopy |
| Zdroj: | Journal of Natural Products. 82:3056-3064 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | Three new germacrane sesquiterpenoid-type alkaloids with an unusual Δ8-7,12-lactam moiety, glechomanamides A-C (1-3), and two pairs of 7,12-hemiketal sesquiterpenoid epimers (4a/b, 5a/b) were isolated from Salvia scapiformis. Their structures were elucidated by spectroscopic methods including HRESIMS, IR, UV, and 1D and 2D NMR and also confirmed by single-crystal X-ray diffraction analysis. The chemical transformation of compounds 1-5 in a solution environment was analyzed by 2D NMR spectroscopy. The aza acetallactams (1-3) were stable in organic solvent, while single crystals of the hemiacetal esters (4a/b, 5a/b) underwent a tautomeric equilibrium after being dissolved. Single crystals of 4a, 4b, and 5a were obtained for the first time as their naturally occurring forms. Glechomanamide B (2) exhibited antiangiogenic activity by suppression of vascular endothelial growth factor (VEGF)-induced tube formation through modulation of VEGF receptor 2 (VEGFR2)-mediated signaling pathways in human umbilical vascular endothelial cells (HUVECs). In addition, compound 2 also showed the significant suppression of mRNA expression associated with glycolysis and angiogenesis biomarkers in high glucose (30 mM)-induced HUVECs. These findings suggest that compound 2 might be a potential lead compound candidate for the management of diabetic retinopathy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|