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Structures and Bioactivities of Quadrangularisosides A, A 1 , B, B 1 , B 2 , C, C 1 , D, D 1 -D 4 , and E from the Sea Cucumber Colochirus quadrangularis : The First Discovery of the Glycosides, Sulfated by C-4 of the Terminal 3- O -Methylglucose Residue. Synergetic Effect on Colony Formation of Tumor HT-29 Cells of these Glycosides with Radioactive Irradiation.
- Source :
-
Marine drugs [Mar Drugs] 2020 Jul 28; Vol. 18 (8). Date of Electronic Publication: 2020 Jul 28. - Publication Year :
- 2020
-
Abstract
- Thirteen new mono-, di-, and trisulfated triterpene glycosides, quadrangularisosides A-D <subscript>4</subscript> ( 1-13 ) have been isolated from the sea cucumber Colochirus quadrangularis, which was collected in Vietnamese waters. The structures of these glycosides were established by 2D NMR spectroscopy and HR-ESI (High Resolution Electrospray Ionization) mass spectrometry. The novel carbohydrate moieties of quadrangularisosides D-D <subscript>4</subscript> ( 8 - 12 ), belonging to the group D, and quadrangularisoside E ( 13 ) contain three sulfate groups, with one of them occupying an unusual position-at C(4) of terminal 3- O -methylglucose residue. Quadrangularisosides A ( 1 ) and D <subscript>3</subscript> ( 11 ) as well as quadrangularisosides A <subscript>1</subscript> ( 2 ) and D <subscript>4</subscript> ( 12 ) are characterized by the new aglycones having 25-hydroperoxyl or 24-hydroperoxyl groups in their side chains, respectively. The cytotoxic activities of compounds 1 - 13 against mouse neuroblastoma Neuro 2a, normal epithelial JB-6 cells, erythrocytes, and human colorectal adenocarcinoma HT-29 cells were studied. All the compounds were rather strong hemolytics. The structural features that most affect the bioactivity of the glycosides are the presence of hydroperoxy groups in the side chains and the quantity of sulfate groups. The membranolytic activity of monosulfated quadrangularisosides of group A ( 1 , 2 ) against Neuro 2a, JB-6 cells, and erythrocytes was relatively weak due to the availability of the hydroperoxyl group, whereas trisulfated quadrangularisosides D <subscript>3</subscript> ( 11 ) and D <subscript>4</subscript> ( 12 ) with the same aglycones as 1 , 2 were the least active compounds in the series due to the combination of these two structural peculiarities. The erythrocytes were more sensitive to the action of the glycosides than Neuro 2a or JB-6 cells, but the structure-activity relationships observed for glycosides 1 - 13 were similar in the three cell lines investigated. The compounds 3 - 5 , 8 , and 9 effectively suppressed the cell viability of HT-29 cells. Quadrangularisosides A <subscript>1</subscript> ( 2 ), C ( 6 ), C <subscript>1</subscript> ( 7 ), and E ( 13 ) possessed strong inhibitory activity on colony formation in HT-29 cells. Due to the synergic effects of these glycosides (0.02 μM) and radioactive irradiation (1 Gy), a decreasing of number of colonies was detected. Glycosides 1 , 3, and 9 enhanced the effect of radiation by about 30%.
- Subjects :
- Animals
Antineoplastic Agents chemistry
Antineoplastic Agents isolation & purification
Colonic Neoplasms pathology
Dose-Response Relationship, Drug
Erythrocytes drug effects
Glycosides chemistry
Glycosides isolation & purification
HT29 Cells
Hemolysis drug effects
Humans
Mice
Molecular Structure
Neuroblastoma drug therapy
Neuroblastoma pathology
Radiation-Sensitizing Agents chemistry
Radiation-Sensitizing Agents isolation & purification
Structure-Activity Relationship
Triterpenes chemistry
Triterpenes isolation & purification
Antineoplastic Agents pharmacology
Cell Proliferation drug effects
Colonic Neoplasms drug therapy
Glycosides pharmacology
Radiation-Sensitizing Agents pharmacology
Sea Cucumbers chemistry
Triterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1660-3397
- Volume :
- 18
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Marine drugs
- Publication Type :
- Academic Journal
- Accession number :
- 32731458
- Full Text :
- https://doi.org/10.3390/md18080394