Mechanisms of Action of Sea Cucumber Triterpene Glycosides Cucumarioside A-1 and Djakonovioside A Against Human Triple-Negative Breast Cancer.

Breast cancer is the most prevalent form of cancer in women worldwide. Triple-negative breast cancer is the most unfavorable for patients, but it is also the most sensitive to chemotherapy. Triterpene glycosides from sea cucumbers possess a high therapeutic potential as anticancer agents.

The Composition of Triterpene Glycosides in the Sea Cucumber : Anticancer Activity of the Glycosides against Three Human Breast Cancer Cell Lines and Quantitative Structure-Activity Relationships (QSAR).

Eight sulfated triterpene glycosides, peronioside A () and psolusosides A (), B (), G (), I (), L (), N () and P (), were isolated from the sea cucumber . Peronioside A () is a new glycoside, while compounds - were found previously in , indicating the phylogenetic and systematic closeness of these species of sea cucumbers. The activity of - against human erythrocytes and their cytotoxicity against the breast cancer cell lines MCF-7, T-47D and triple-negative MDA-MB-231 were tested.

Anticancer Activity of the Marine Triterpene Glycoside Cucumarioside A-2 in Human Prostate Cancer Cells.

Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), treatment is inevitably hampered by the development of drug resistance. Thus, new drugs are urgently needed. We investigated the efficacy, toxicity, and mechanism of action of the marine triterpene glycoside cucumarioside A-2 (CA-2) using an in vitro CRPC model.

Fucosylated Chondroitin Sulfates with Rare Disaccharide Branches from the Sea Cucumbers and : Structures and Influence on Hematopoiesis.

Two fucosylated chondroitin sulfates were isolated from the sea cucumbers and using a conventional extraction procedure in the presence of papain, followed by anion-exchange chromatography on DEAE-Sephacel. Their composition was characterized in terms of quantitative monosaccharide and sulfate content, and structures were mainly elucidated using 1D- and 2D-NMR spectroscopy. As revealed by the data of the NMR spectra, both polysaccharides along with the usual fucosyl branches contained rare disaccharide branches α-D-GalNAc46-(1→2)-α-L-Fuc34 → attached to -3 of the GlcA of the backbone ( = H or SO).

Sulfated Triterpene Glycosides from the Far Eastern Sea Cucumber : Djakonoviosides C, D, E, and F; Cytotoxicity against Human Breast Cancer Cell Lines; Quantitative Structure-Activity Relationships.

Four new mono- and trisulfated triterpene penta- and tetraosides, djakonoviosides C (), D (), E (), and F () were isolated from the Far Eastern sea cucumber (Cucumariidae, Dendrochirotida), along with six known glycosides found earlier in other species. The structures of unreported compounds were established on the basis of extensive analysis of 1D and 2D NMR spectra as well as by HR-ESI-MS data. The set of compounds contains six different types of carbohydrate chains including two new ones.

A Mass Spectrometry Database for Sea Cucumber Triterpene Glycosides.

Sea cucumber triterpene glycosides are a class of secondary metabolites that possess distinctive chemical structures and exhibit a variety of biological and pharmacological activities. The application of MS-based approaches for the study of triterpene glycosides allows rapid evaluation of the structural diversity of metabolites in complex mixtures. However, the identification of the detected triterpene glycosides can be challenging.

Djakonoviosides A, A, A, B-B - Triterpene Monosulfated Tetra- and Pentaosides from the Sea Cucumber : The First Finding of a Hemiketal Fragment in the Aglycones; Activity against Human Breast Cancer Cell Lines.

Seven new monosulfated triterpene glycosides, djakonoviosides A (), A (), A (), and B-B (-), along with three known glycosides found earlier in the other species, namely okhotoside A-1, cucumarioside A-1, and frondoside D, have been isolated from the far eastern sea cucumber (Cucumariidae, Dendrochirotida). The structures were established on the basis of extensive analysis of 1D and 2D NMR spectra and confirmed by HR-ESI-MS data. The compounds of groups A and B differ from each other in their carbohydrate chains, namely monosulfated tetrasaccharide chains are inherent to group A and pentasaccharide chains with one sulfate group, branched by C-2 Qui2, are characteristic of group B.

Chilensosides E, F, and G-New Tetrasulfated Triterpene Glycosides from the Sea Cucumber (Caudinidae, Molpadida): Structures, Activity, and Biogenesis.

Three new tetrasulfated triterpene glycosides, chilensosides E (), F (), and G (), have been isolated from the Far-Eastern sea cucumber (Caudinidae, Molpadida). The structures were established based on extensive analysis of 1D and 2D NMR spectra and confirmed by HR-ESI-MS data. The compounds differ in their carbohydrate chains, namely in the number of monosaccharide residues (five or six) and in the positions of sulfate groups.

The Isolation, Structure Elucidation and Bioactivity Study of Chilensosides A, A, B, C, and D, Holostane Triterpene Di-, Tri- and Tetrasulfated Pentaosides from the Sea Cucumber (Caudinidae, Molpadida).

Five new triterpene (4,4,14-trimethylsterol) di-, tri- and tetrasulfated pentaosides, chilensosides A (), A (), B (), C (), and D () were isolated from the Far-Eastern sea cucumber . The structures were established on the basis of extensive analysis of 1D and 2D NMR spectra and confirmed by HR-ESI-MS data. The structural variability of the glycosides concerned the pentasaccharide chains.

Structures and Biologic Activity of Chitonoidosides I, J, K, K and L-Triterpene Di-, Tri- and Tetrasulfated Hexaosides from the Sea Cucumber .

Five new triterpene di-, tri- and tetrasulfated hexaosides (chitonoidosides I (), J (), K (), K () and L ()) were isolated from the Far-Eastern sea cucumber , collected near Bering Island (Commander Islands) from a depth of 100-150 m. The structural variability of the glycosides concerned both the aglycones (with 7(8)- or 9(11)-double bonds) and carbohydrate chains differing from each other by the third sugar residue (Xyl or sulfated by C-6 Glc) and/or by the fourth-terminal in the bottom semi-chain-residue (Glc or sulfated by C-6 MeGlc) as well as by the positions of a sulfate group at C-4 or C-6 in the sixth-terminal in the upper semi-chain-residue (MeGlc). Hemolytic activities of these compounds - against human erythrocytes as well as cytotoxicity against human cancer cell lines, HeLa, DLD-1 and HL-60, were studied.

Triterpene Glycosides from the Far Eastern Sea Cucumber : Chemical Structures and Cytotoxicities of Chitonoidosides E, F, G, and H.

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 ().

Structure-Activity Relationships of Holothuroid's Triterpene Glycosides and Some In Silico Insights Obtained by Molecular Dynamics Study on the Mechanisms of Their Membranolytic Action.

The article describes the structure-activity relationships (SAR) for a broad series of sea cucumber glycosides on different tumor cell lines and erythrocytes, and an in silico modulation of the interaction of selected glycosides from the sea cucumber with model erythrocyte membranes using full-atom molecular dynamics (MD) simulations. The in silico approach revealed that the glycosides bound to the membrane surface mainly through hydrophobic interactions and hydrogen bonds. The mode of such interactions depends on the aglycone structure, including the side chain structural peculiarities, and varies to a great extent.

Unusual Structures and Cytotoxicities of Chitonoidosides A, A, B, C, D, and E, Six Triterpene Glycosides from the Far Eastern Sea Cucumber .

Six new triterpene tetra-, penta- and hexaosides, chitonoidosides A (), A (), B (), C (), D (), and E (), containing one or two sulfate groups, have been isolated from the Far-Eastern sea cucumber , collected near Bering Island (Commander Islands) from the depth of 100-150 m. Three of the isolated compounds (, and ) are characterized by the unusual aglycone of new type having 18(20)-ether bond and lacking a lactone in contrast with wide spread holostane derivatives. Another unexpected finding is 3--methylxylose residue as a terminal unit in the carbohydrate chains of chitonoidosides B (), C (), and E (), which has never been found before in the glycosides from holothurians belonging to the family.

Triterpene Glycosides from the Far Eastern Sea Cucumber (Levin): The Structures, Cytotoxicities, and Biogenesis of Kurilosides A, D, G, H, I, I, J, K, and K.

Nine new mono-, di-, and trisulfated triterpene penta- and hexaosides, kurilosides A (), D (), G (), H (), I (), I (), J (), K (), and K () and two desulfated derivatives, DS-kuriloside L (), having a trisaccharide branched chain, and DS-kuriloside M (), having hexa--lanostane aglycone with a 7(8)-double bond, have been isolated from the Far-Eastern deep-water sea cucumber (Levin) and their structures were elucidated based on 2D NMR spectroscopy and HR-ESI mass-spectrometry. Five earlier unknown carbohydrate chains and two aglycones (having a 16,(20S)-dihydroxy-fragment and a 16-acetoxy,(20S)-hydroxy fragment) were found in these glycosides. All the glycosides - have a sulfate group at C-6 Glc, attached to C-4 Xyl1, while the positions of the other sulfate groups vary in different groups of kurilosides.

Kurilosides A, A, C, D, E and F-Triterpene Glycosides from the Far Eastern Sea Cucumber (Levin): Structures with Unusual Non-Holostane Aglycones and Cytotoxicities.

Six new monosulfated triterpene tetra-, penta- and hexaosides, namely, the kurilosides A (), A (), C (), D (), E () and F (), as well as the known earlier kuriloside A (), having unusual non-holostane aglycones without lactone, have been isolated from the sea cucumber (Levin) (Cucumariidae, Dendrochirotida) collected in the Sea of Okhotsk near Onekotan Island from a depth of 100 m. Structures of the glycosides were established by 2D NMR spectroscopy and HR-ESI mass spectrometry. Kurilosides of the groups A and E contain carbohydrate moieties with a rare architecture (a pentasaccharide branched by C(4) Xyl1), differing from each other in the second monosaccharide residue (quinovose or glucose, correspondingly); kurilosides of the group C are characterized by a unique tetrasaccharide branched by a C(4) Xyl1 sugar chain; and kurilosides of the groups D and F are hexaosides differing from each other in the presence of an -methyl group in the fourth (terminal) sugar unit.

Structures and Bioactivities of Quadrangularisosides A, A, B, B, B, C, C, D, D-D, and E from the Sea Cucumber : The First Discovery of the Glycosides, Sulfated by C-4 of the Terminal 3--Methylglucose Residue. Synergetic Effect on Colony Formation of Tumor HT-29 Cells of these Glycosides with Radioactive Irradiation.

Thirteen new mono-, di-, and trisulfated triterpene glycosides, quadrangularisosides A-D () have been isolated from the sea cucumber 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 (-), belonging to the group D, and quadrangularisoside E () contain three sulfate groups, with one of them occupying an unusual position-at C(4) of terminal 3--methylglucose residue.

Structures and Bioactivities of Psolusosides B, B, J, K, L, M, N, O, P, and Q from the Sea Cucumber . The First Finding of Tetrasulfated Marine Low Molecular Weight Metabolites.

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.

Structures and Bioactivities of Six New Triterpene Glycosides, Psolusosides E, F, G, H, H, and I and the Corrected Structure of Psolusoside B from the Sea Cucumber .

Seven sulfated triterpene glycosides, psolusosides B (), E (), F (), G (), H (), H (), and I (), along with earlier known psolusoside A and colochiroside D have been isolated from the sea cucumber collected in the Sea of Okhotsk. Herein, the structure of psolusoside B (), elucidated by us in 1989 as a monosulfated tetraoside, has been revised with application of modern NMR and particularly MS data and proved to be a disulfated tetraoside. The structures of other glycosides were elucidated by 2D NMR spectroscopy and HR-ESI mass-spectrometry.

Non-holostane aglycones of sea cucumber triterpene glycosides. Structure, biosynthesis, evolution.

Triterpene glycosides are known as characteristic metabolites of sea cucumbers (class Holothuroidea, phylum Echinodermata). The most of them have lanostane aglycones containing 18(20)-lactone, i.e.

Cladolosides O, P, P-P and R, triterpene glycosides with two novel types of carbohydrate chains from the sea cucumberCladolabes schmeltzii. Inhibition of cancer cells colony formation and its synergy with radioactive irradiation.

The sea cucumber Cladolabes schmeltzii (Sclerodactylidae, Dendrochirotida) contains diverse glycosides, including several dozen individual compounds. Six new triterpene oligoglycosides, cladolosides O (1), P (2), P (3), P (4), P (5) and R (6), were isolated from this sea cucumber. Their structures were elucidated by 2D NMR spectroscopy and HR ESI mass spectrometry.

Cladolosides C, D, D, M, M, M, N and Q, new triterpene glycosides with diverse carbohydrate chains from sea cucumber Cladolabes schmeltzii. An uncommon 20,21,22,23,24,25,26,27-okta-nor-lanostane aglycone. The synergism of inhibitory action of non-toxic dose of the glycosides and radioactive irradiation on colony formation of HT-29 cancer cells.

Eight new triterpene olygoglycosides, cladolosides C (1), D (2), D (3), M (4), M (5), M (6), N (7) and Q (8), were isolated from the tropical Indo-West Pacific sea cucumber Cladolabes schmeltzii (Sclerodactylidae, Dendrochirotida). Structures of these glycosides were elucidated by 2D NMR spectroscopy and HR ESI mass spectrometry. A novel hexasaccharide carbohydrate chain having xylose residues as the first, second and third sugars was found in the glycoside 7.

Cucumarioside A₂-2 Causes Macrophage Activation in Mouse Spleen.

The immunomodulatory effect of triterpene glycoside cucumarioside A₂-2 (CA₂-2), isolated from the Far Eastern sea cucumber , was compared with lipopolysaccharide (LPS) on mouse spleen. It has been shown that the intraperitoneal () glycoside administration leads to increased spleen macrophage activating markers iba-1, IL-1β, iNOs, ROS and NO formation, with additional change of macrophage phenotype to M1. The mass spectrometry profiles of peptide/protein were obtained using MALDI-TOF-MS on the different parts of spleen sections isolated by laser mircodissection techniques.

Metabolite Profiling of Triterpene Glycosides of the Far Eastern Sea Cucumber Eupentacta fraudatrix and Their Distribution in Various Body Components Using LC-ESI QTOF-MS.

The Far Eastern sea cucumber is an inhabitant of shallow waters of the south part of the Sea of Japan. This animal is an interesting and rich source of triterpene glycosides with unique chemical structures and various biological activities. The objective of this study was to investigate composition and distribution in various body components of triterpene glycosides of the sea cucumber .

Nine New Triterpene Glycosides, Magnumosides A₁-A₄, B₁, B₂, C₁, C₂ and C₄, from the Vietnamese Sea Cucumber Neothyonidium (=Massinium) magnum: Structures and Activities against Tumor Cells Independently and in Synergy with Radioactive Irradiation.

Nine new sulfated triterpene glycosides, magnumosides A₁ (), A₂ (), A₃ (), A₄ (), B₁ (), B₂ (), C₁ (), C₂ () and C₄ () as well as a known colochiroside B₂ () have been isolated from the tropical Indo-West Pacific sea cucumber (=) (Phyllophoridae, Dendrochirotida) collected in the Vietnamese shallow waters. The structures of new glycosides were elucidated by 2D NMR spectroscopy and mass-spectrometry. All the isolated new glycosides were characterized by the non-holostane type lanostane aglycones having 18(16)-lactone and 7(8)-double bond and differed from each other by the side chains and carbohydrate moieties structures.

Frondoside A induces AIF-associated caspase-independent apoptosis in Burkitt lymphoma cells.

For patients with refractory or relapsed Burkitt lymphoma (BL), no standard therapy is available for second-line treatment to date. Nonfunctional caspases-dependent apoptosis pathways, inactivating p53 mutations and pro-survival autophagy prevent activity of conventional chemotherapy. Thus, new drugs bypassing these mechanisms of resistance are required.