Triterpene glycosides are characteristic metabolites of sea cucumbers (Holothurioidea, Echinodermata). The majority of the glycosides belong to the holostane type {lanostane derivatives with an ...18(20)-lactone}. Carbohydrate chains of these glycosides contain xylose, glucose, quinovose, 3-O-methylglucose, and, rarely, 3-O-methylxylose, 3-O-methylglucuronic acid, 3-O-methylquinovose, and 6-O-acetyl-glucose. The glycosides are specific for genera, groups of genera and even for species. The advantages and problems in the use of triterpene glycosides as taxonomic markers in the systematics of sea cucumbers are discussed.
Four new triterpene disulfated glycosides, chitonoidosides E
(
), F (
), G (
), and H (
), were isolated from the Far-Eastern sea cucumber
and collected near Bering Island (Commander Islands) at ...depths of 100-150 m. Among them there are two hexaosides (
and
), differing from each other by the terminal (sixth) sugar residue, one pentaoside (
) and one tetraoside (
), characterized by a glycoside architecture of oligosaccharide chains with shortened bottom semi-chains, which is uncommon for sea cucumbers. Some additional distinctive structural features inherent in
-
were also found: the aglycone of a recently discovered new type, with 18(20)-ether bond and lacking a lactone in chitonoidoside G (
), glycoside 3-
-methylxylose residue in chitonoidoside E
(
), which is rarely detected in sea cucumbers, and sulfated by uncommon position 4 terminal 3-
-methylglucose in chitonoidosides F (
) and H (
). The hemolytic activities of compounds
-
and chitonoidoside E against human erythrocytes and their cytotoxic action against the human cancer cell lines, adenocarcinoma HeLa, colorectal adenocarcinoma DLD-1, and monocytes THP-1, were studied. The glycoside with hexasaccharide chains (
,
and chitonoidoside E) were the most active against erythrocytes. A similar tendency was observed for the cytotoxicity against adenocarcinoma HeLa cells, but the demonstrated effects were moderate. The monocyte THP-1 cell line and erythrocytes were comparably sensitive to the action of the glycosides, but the activity of chitonoidosides E and E
(
) significantly differed from that of
in relation to THP-1 cells. A tetraoside with a shortened bottom semi-chain, chitonoidoside F (
), displayed the weakest membranolytic effect in the series.
Six new monosulfated triterpene glycosides, cladolosides I1 (1), I2 (2), J1 (3), K1 (4), K2 (5) and L1 (6) were isolated from the tropical Indo-West Pacific sea cucumber Cladolabes schmeltzii ...(Cladolabinae, Sclerodactylidae, Dendrochirotida). Structures of these glycosides were elucidated by 2D NMR spectroscopy and mass spectrometry. Four new types of carbohydrate chains have been found in 1–6. Cladolosides of the groups I and J are characterized by pentasaccharide carbohydrate chains sulfated at a terminal 3-O-methylglucose residue and branched by the position 4 of the first xylose residue, but differing from each other in the lengths of the main and side carbohydrate chains. Cladolosides of the groups K and L contain hexasaccharide chains with different positions of a sulfated terminal 3-O-methylglucose residue (as the fourth or the sixth monosaccharide residue). Sulfated hexasaccharide carbohydrate chains were found in the sea cucumbers glycosides for the first time. A pentasaccharide carbohydrate chain of cladoloside J1 (3) having a disaccharide moiety of glucose and a sulfated 3-O-methylglucose linked to the first xylose residue in a linear trisaccharide fragment is also unusual. All substances studied demonstrated strong or moderate hemolytic and cytotoxic effects.
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•Six new monosulfated triterpene glycosides were isolated from Cladolabes schmeltzii.•Two new pentasaccharide and two new hexasaccharide carbohydrate chains were found.•The presence of a sulfate in hexaosides is unique for sea cucumber glycosides.
Triterpene glycosides isolated from holothurians are natural products known to possess cytotoxic properties against cancer cells. However, their anticancer prophylactic activity has not been studied ...sufficiently. The anticancer prophylactic; cytotoxic, and pro-apoptotic properties of 18 triterpene glycosides, as well as their effects on the transcriptional activities of activator protein-I (AP-1) and nuclear factor-KB (NF-KB), were examined using methods that included EGF-induced JB6 C141 P' cell transformation in soft agar, flow cytometry, MTS assessment of cell viability, and a luciferase activity assay. The compounds inhibited EGF-induced neoplastic JB6 C141 P' cell transformation in soft agar and caused apoptosis and necrosis of human HL-60 and THP-I leukemia cells. AP- and NF-KB were involved in the cellular response to the treatment by the compounds. Conclusion: glycosides isolated from holothurians of Cucumariidae, Stichopodidae, Psolidae, Holothuriidae and Synaptidae families have potential for development as new antitumor agents and as instruments to study AP-I and NF-kB.
Eight new nonsulfated triterpene glycosides, cladolosides C3 (1), E1 (2), E2 (3), F1 (4), F2 (5), G (6), H1 (7) and H2 (8) have been isolated from the tropical Indo-West Pacific sea cucumber ...Cladolabes schmeltzii (Cladolabinae, Sclerodactylidae, Dendrochirotida) collected in the Vietnamese shallow waters. The structures of the glycosides were elucidated by 2D NMR spectroscopy and mass-spectrometry. Glycosides 2, 3, 4, and 5 have pentasaccharide branched carbohydrate moieties and differ from each other by monosaccharide compositions and aglycone structures. At that, glycosides 2 and 3 contain three xylose, one 3-O-methyl-glucose and one quinovose residues, while glycosides 4 and 5 have two quinovose, two xylose and one 3-O-methyl-glucose residues. Compounds 1 and 6–8 are hexaosides differing from each other by aglycone structures and by the fifth monosaccharide residue, which proved to be glucose in cladoloside C3 (1), xylose in cladoloside G (6) and quinovose in cladolosides H1 (7) and H2 (8). The presence of quinovose residue in the fifth position, as in 4, 5, 7 and 8 has never been earlier found in carbohydrate chains of triterpene glycosides from sea cucumbers. The carbohydrate chains with xylose in the fifth position of pentaosides and hexaosides are also very unusual for holothurious glycosides. All the substances demonstrate strong or moderate cytotoxic and hemolytic effects with hexaosides being more active than the corresponding pentaosides. Peculiarities of the biosynthesis and biochemical evolution of glycosides of this type are discussed.
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•Eight new nonsulfated triterpene glycosides were isolated from Cladolabes schmeltzii.•Four new pentasaccharide and three hexasaccharide carbohydrate chains were found.•The presence of quinovose as fifth sugar is unique.
Six new monosulfated triterpene glycosides, cladolosides I
(1), I
(2), J
(3), K
(4), K
(5) and L
(6) were isolated from the tropical Indo-West Pacific sea cucumber Cladolabes schmeltzii ...(Cladolabinae, Sclerodactylidae, Dendrochirotida). Structures of these glycosides were elucidated by 2D NMR spectroscopy and mass spectrometry. Four new types of carbohydrate chains have been found in 1-6. Cladolosides of the groups I and J are characterized by pentasaccharide carbohydrate chains sulfated at a terminal 3-O-methylglucose residue and branched by the position 4 of the first xylose residue, but differing from each other in the lengths of the main and side carbohydrate chains. Cladolosides of the groups K and L contain hexasaccharide chains with different positions of a sulfated terminal 3-O-methylglucose residue (as the fourth or the sixth monosaccharide residue). Sulfated hexasaccharide carbohydrate chains were found in the sea cucumbers glycosides for the first time. A pentasaccharide carbohydrate chain of cladoloside J
(3) having a disaccharide moiety of glucose and a sulfated 3-O-methylglucose linked to the first xylose residue in a linear trisaccharide fragment is also unusual. All substances studied demonstrated strong or moderate hemolytic and cytotoxic effects.
Seven eremophilane-type sesquiterpene glucosides, alticolosides A-G, have been isolated from aerial parts of the endemic Far Eastern species Ligularia alticola Worosch. (Family Asteraceae) along with ...two known compounds, monoterpenoid glycoside (4S)-α-terpineol 8-O-β-D-glucopyranoside and norditerpenoid glycoside 7(8)-dihydro-β-ionone 3-O-β-D-glucopyranoside. Alticoloside D was identified with the earlier known 8-O-(β-D-glucopyranosyl)-2-oxo-eremophila-1(10),8,11-triene, but the stereostructure of the latter was revised on the basis of ROESY and CD data. All the glycosides are derivatives of new eremophilane-type aglycones, differing from known eremophilanes in details of planar and/or stereo structures except for the aglycone of alticoloside E.
Ten new di-, tri- and tetrasulfated triterpene glycosides, psolusosides B
(
), B
(
), J (
), K (
), L (
), M (
), N (
), O (
), P (
), and Q (
), were isolated from the sea cucumber
collected in the ...Sea of Okhotsk near the Kurile Islands. Structures of these glycosides were established by two-dimensional (2D) NMR spectroscopy and HR-ESI mass-spectrometry. It is particularly interesting that highly polar compounds
and
contain four sulfate groups in their carbohydrate moieties, including two sulfates in the same terminal glucose residue. Glycoside
has an unusual non-holostane aglycone with 18(16)-lactone and a unique 7,8-epoxy fragment. Cytotoxic activities of compounds
-
against several mouse cell lines such as Ehrlich ascites carcinoma cells, neuroblastoma Neuro 2A, normal epithelial JB-6 cells, and erythrocytes were quite different depending both on structural peculiarities of these glycosides and the type of cells subjected to their actions. Psolusoside L (
), pentaoside, with three sulfate groups at C-6 of two glucose and one 3-
-methylglucose residue and holostane aglycone, is the most active compound in the series. The presence of a sulfate group at C-2 of the terminal glucose residue attached to C-4 of the first (xylose) residue significantly decreases activities of the corresponding glycosides. Psolusosides of group B (
,
and known psolusoside B) are inactive in all tests due to the presence of non-holostane aglycones and tetrasaccharide-branched sugar chains sulfated by C-2 of Glc4.
Two novel triterpene holostane glycosides, synaptosides A (1) and A1 (2), have been isolated from the Vietnamese sea cucumber Synapta maculata (Synaptida, Apodida). Their structures were elucidated ...by spectroscopic methods (NMR and MS) and chemical transformations. Glycosides 1 and 2 have rare branched pentasaccharide carbohydrate chains featuring a 3-O-methylglucuronic acid residue not previously reported in glycosides from sea cucumbers and a 6-O-sulfated glucose. Glycoside 2 has an oxo group at C-7 and a 8(9)-double bond. All these structural features are unknown in glycosides from sea cucumbers. Glycoside 1 has moderate cytotoxic activity (IC50 8.6 µg/mL) and glycoside 2 is inactive against HeLa tumor cells.
A novel oligoglycoside cucumarioside A8 with unprecedented hydroxy group at C-18 was isolated from sea cucumber Eupentacta fraudatrix and its structure elucidated. The presence of hydroxy group at ...C-18 indicates that the glycoside is a “hot” metabolite that allows clarification of some peculiarities of 4,4,14-trimethylsterol glycoside biosynthetic pathways. A hypothetical scheme of biosynthesis of triterpene glycosides in sea cucumbers is proposed where direct formation of lanostane derivatives with a 7(8)-double bond from prosteroid cation is possible.
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► New minor 4,4,14-trimethylsterol glycoside with unprecedented hydroxyl group at C-18 has been isolated from Eupentacta fraudatrix. ► Its structure allows to clarify some peculiarities of glycoside biosynthesis. ► Aglycone moiety biosynthesis does not precede glycosylation, but is concurrent. ► 9β-H configuration and type of unsaturation are formed in early biosynthetic stages.
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