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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 1 (3), P 2 (4), P 3 (5) and R (6), were isolated from this sea cucumber. Their structures were elucidated by 2D NMR spectroscopy and HR ESI mass spectrometry. Cladoloside O (1) has a pentasaccharide carbohydrate chain. Cladolosides of the group P and cladoloside R (6) include novel hexasaccharide carbohydrate chains with different positions of non-methylated terminal sugar units. All the isolated compounds demonstrate strong cytotoxic activities against cells of mouse Ehrlich carcinoma cells (ascite form) and mouse erythrocytes. The cytotoxicity of these compounds against human colorectal adenocarcinoma HT-29 cells was somewhat lower. The compounds 1-6 also inhibit the colony formation and growth of HT-29 cells at non-cytotoxic concentrations. The highest inhibition effect was demonstrated by cladoloside P 1 (3). Moreover, synergism of effects of radioactive irradiation and non-toxic dose of compounds 1-6 on colony formation of HT-29 cells was observed. Cladolosides P 2 (4) and P 3 (5) were the most active and increased the inhibitory effect of radiation by more than 70%. The metabolic network demonstrating the biosynthetic pathways to carbohydrate chains of the glycosides of C. schmeltzii, based on a comparison of their structures, was constructed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Eight new triterpene olygoglycosides, cladolosides C 4 (1), D 1 (2), D 2 (3), M (4), M 1 (5), M 2 (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. Cladoloside C 4 (1) contains an uncommon 20,21,22,23,24,25,26,27-octa-norlanostane aglycone. Cladolosides D 1 (2), D 2 (3) and Q (8) were new representatives of the hexaosides with a non-methylated terminal sugar unit in the "upper" half-chain. Cytotoxic activities of the isolated compounds against ascite form of mouse Ehrlich carcinoma cells, mouse erythrocytes and human colorectal adenocarcinoma HT-29 cells were examined and their structure-activity relationships were analyzed. In addition, the majority of tested compounds, except for cladoloside D 2 (3), inhibited the colony formation and growth of HT-29 cells at non-cytotoxic concentrations. The highest inhibitory activity was demonstrated by cladoloside M 1 (5). Moreover, synergism of effects of radioactive irradiation and non-toxic dose of compounds 1-8 decreasing the number of colonies of HT-29 cells was observed. Cladoloside N (7) was the most active and increased the inhibitory effect from radiation by 75%. The biosynthetic transformations of the aglycones are discussed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Six new monosulfated triterpene glycosides, cladolosides I 1 (1), I 2 (2), J 1 (3), K 1 (4), K 2 (5) and L 1 (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 1 (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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Four new trisulfated triterpene glycosides, fallaxosides D₄ (1), D₅ (2), D₆ (3) and D₇ (4) have been isolated from the sea cucumber Cucumaria fallax (Cucumariidae, Dendrochirotida). The structures of the glycosides have been elucidated by 2D NMR spectroscopy and HRESIMS. All the glycosides have the lanostane aglycones of a rare non-holostane type with 7(8)-, 8(9)- or 9(11)-double bonds, one or two hydroxyl groups occupying unusual positions in the polycyclic nucleus and shortened or normal side chains. The pentasaccharide carbohydrate moieties of 1-4 have three sulfate groups. The cytotoxic activity of glycosides 1-4 against the ascite form of mouse Ehrlich carcinoma cells and mouse spleen lymphocytes and hemolytic activity against mouse erythrocytes have been studied.

Four hew triterpene glycosides, fallaxosides C, (1), C2 (2), D, (3) and D2 (4) along with the known cucumarioside A3-2 (5) and koreoside A (6) have-been isolated from the sea cucumber Cucumaria fallax (Cucumariidae, Dendrochirotida). Structures of the glycosides have been elucidated by 2D NMR spectroscopy and mass spectrometry. All of the glycosides are rare non-holostane derivatives having shortened side chains and contain pentasaccharide carbohydrate moieties with two or three sulfate groups. Structures of these triterpene glycosides and their comparison with those earlier isolated from Cucuniaria spp. and Pseudocnus dubiosus leoninus allow us to suggest that the present assignment of C. fallax to the genus Pseudocnus is not correct, and this species.should be assigned to the genus Cucumaria. Cytotoxic activity of glycosides 1-5 against the ascite form of mouse Ehrlich carcinoma cells and mouse spleen lymphocytes and hemolytic activity against mouse erythrocytes have been studied. The glycosides were expectedly not active in all the tests due to the absence of an 18(20)-lactone in their aglycones and the presence of several sulfate groups. There was one exception, cucumarioside A₃-2 (5), which. demonstrated a weak cytotoxicity against lymphocytes and moderate hemolytic activity.

The unusual non-holostane triterpene glycoside, colochiroside E (1) was isolated from the sea cucumber Colochirus robustus (Cucumariidae, Dendrochirotida). The structure of 1 was established by analysis of 1D, 2D NMR and HRESI MS data. Colochiroside E (1) belongs to a rare group of glycosylated 9β-H-lanosta-18(16)-lactones and has an unprecedented sulfated trisaccharide carbohydrate chain consisting of two glucose and one xylose units. In contrast with (9β-H)-7(8)-unsaturated holostane glycosides, the 7(8)-double bond in the having (9β-H)-configuration aglycone of colochiroside E is not capable of migration into the 8(9)- and then into the 9(11)-position on treatment with HCl. The formation of a chlorine derivative of 1 was observed under these conditions.

Four new triterpene glycosides, colochirosides A₁ (1), A₂ (2), A₃ (3) and D (4), have been isolated from the sea cucumber Colochirus robustus (Cucumariidae, Dendrochirotida). Structures of the glycosides have been elucidated by 2D NMR spectroscopy and mass-spectrometry. Colochiroside D (4) has a new type of carbohydrate chain having the only sulfate group attached to C-6 of the third (glucose) monosaccharide residue. Cytotoxic activities of glycosides 1-4 against the ascite form of mouse Ehrlich carcinoma cells and hemolytic activity against mouse erythrocytes have been studied. Hemolytic activity of the glycosides was higher than cytotoxic. Glycosides 1, 3 and 4 demonstrated strong effects, whereas compound 2 showed only moderate activity.

Four new triterpene glycosides, colochirosides B1 (1), B2 (2), B3 (3) and C (4) have been isolated from the sea cucumber Colochirus robustus (Cucumariidae, Dendrochirotida). Six known earlier glycosides from representatives of two families of the order Dendrochirotida have also been found in C. robustus. Structures of the glycosides have been elucidated by 2D NMR spectroscopy and mass spectrometry. All the glycosides belong to the holostane series and contain tetrasaccharide linear carbohydrate chains with one or two sulfate groups. Cytotoxic activities of glycosides 1-4 against the ascite form of mouse Ehrlich carcinoma cells and hemolytic activities against mouse erythrocytes have been studied. Hemolytic activity of the glycosides was higher than cytotoxic. Glycosides 3 and 4 demonstrated strong effects, whereas compounds 1 and 2 containing the hydroxy-group in the side chains showed moderate hemolytic activity and were not cytotoxic.

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Six new triterpene glycosides, cladolosides Al-A6 (1-6), have been isolated from the Vietnamese sea cucumber Cladolabes schmeltzii (Cladolabinae, Sclerodactylidae, Dendrochirotida). Structures of the glycosides were elucidated by 2D NMR spectroscopy and MS. All the glycosides have nonsulfated tetrasaccharide linear carbohydrate moieties. Glycoside 6 has a glucose residue as the third monosaccharide unit, while the rest of the compounds comprise a xylose in this postion of the carbohydrate chain. Glycosides 1-6 differ from each other in the structures of their holostane aglycones. Cytotoxic activities of glycosides 1-6 were studied against mouse spleenocytes, along with hemolytic activities against mouse erythrocytes. All the compounds, except cladoloside A5 (5) posessing a hydroxy-group in the aglycone side chain, demonstrated rather strong cytotoxic and hemolytic effects. The most active glycosides were cladolosides A1 (1) and A2 (2) having two O-acetic groups and the xylose residue in the third position of the sugar chain.

Four new triterpene glycosides, violaceusosides C (1), D (2), E (3) and G (4) have been isolated from the sea cucumber Pseudocolochirus violaceus (Cucumariidae, Dendrochirotida). Eight known glycosides, DS-holothurin A and holothurinoside A, isolated earlier from Holothuria forskalii (order Aspidochirotida); and violaceuside A, lefevreoside C, philinopside E, intercedenside B, violaceuside II and liovilloside A isolated earlier from representatives of the family Cucumariidae, order Dendrochirotida have also been found in P. violaceus. The chemical structures of the glycosides were elucidated by 2D NMR spectroscopy and mass spectrometry. Violaceusosides C (1), D (2), E (3) and G (4) have holostane-type aglycones and tetrasaccharide linear carbohydrate chains differing in the sugar composition and the number and position of sulfate groups. Violaceusosides E (3) and G (4) are characterized by the presence of a sulfate group at C-3 of the quinovose residue that is very rare among sea cucumber glycosides. Cytotoxic activities of the glycosides 1-4 against cells of the ascite form of mouse Ehrlich carcinoma and hemolytic activities against mouse erythrocytes have been studied. Violaceusosides C (1) and D (2) demonstrated moderate cytotoxic and hemolytic effects, while violaceusosides E (3) and G (4) have more powerful activities.

Six new nonsulfated triterpene glycosides, cladolosides B1 (1), B2 (2), C (3), C1 (4), C2 (5) and D (6) and known holotoxin A1 (7) have been isolated from the tropical Indo-West Pacific sea cucumber Cladolabes schmeltzii (Cladolabinae, Sclerodactylidae, Dendrochirotida). Structures of the glycosides were elucidated by 2D NMR spectroscopy and mass-spectrometry. Glycosides 1 and 2 have pentasaccharide branched carbohydrate moieties and differ from each other by the aglycone structures. Compounds 3-6 are hexaosides; 3-5 contain identical carbohydrate moieties with two terminal 3-O-methylglucose residues and glucose as the fifth sugar unit and differ from each other in the structures of their aglycones. Cladoloside D (6) has a new variant of carbohydrate chain with xylose and glucose residues as fifth and sixth monosaccharides, correspondingly. All of the substances demonstrated rather strong cytotoxic and hemolytic effects.

Three new minor triterpene glycosides, cucumariosides I1 (1), I3 (2) and I4 (3) have been isolated from the Far Eastern sea cucumber Eupentacta fraudatrix. Structures of the glycosides were elucidated by 2D NMR spectroscopy and MS. Glycosides 1-3 belong to the group of cucumariosides I, havingbranched pentasaccharide carbohydrate moieties with two sulfate groups and possessing 3-O-methyl-D-xylose as a terminal monosaccharide unit that is a characteristic feature of all the glycosides isolated from E. fraudatrix. Glycosides 1 and 2 differ from each other by the side chain structures in the holostane aglycone moieties, while cucumarioside I4 (3) has a 23, 24, 25, 26, 27-pentanorlanostane aglycone with an 18 (16)-lactone. Cytotoxic activities of glycosides 1-3 against mouse spleen lymphocytes and ascite form of mouse Ehrlich carcinoma cells, along with hemolytic activity against mouse erythrocytes and antifungal activity were studied. Glycoside 1, having an aglycone side chain with a 24 (25)-double bond, possesses moderate activity in all the tests, while glycoside 2, having 23 (24)-double bond and 25-hydroxy group in the side chain, and glycoside 3 with an aglycone with an 18 (16)-lactone and shortened side chain have either low activity or are non-active.

Five new minor triterpene glycosides, typicosides A1 (1), A2 (2), B1 (3), C1 (4) and C2 (5), along with two known glycosides, intercedenside A and holothurin B3, have been isolated from the sea cucumber Actinocucumis typica. Structures of the glycosides were elucidated by 2D NMR spectroscopy andMS. Glycosides 1-5 are linear mono- and disulfated tetraosides differing from each other in both aglycone structures and monosaccharide composition of the carbohydrate chains. Typicosides A1 (1) and A2 (2) have identical monosulfated carbohydrate moieties with a xylose residue as the third monosaccharide unit and differ from each other in aglycon structures. Typicoside B1 (3) has glucose as the third monosaccharide residue. Typicosides C1 (4) and C2 (5) contain the same disulfated carbohydrate chains and differ from each other in structures of aglycone side chains. Antifungal activity of glycosides 1-5 against three species of fungi along with cytotoxic activity against mouse spleen lymphocytes and mouse Ehrlich carcinoma cells (ascite form), as well as hemolytic activities against mouse erythrocytes have been studied. All new glycosides, except for typicoside C1 (4), containing a hydroxy-group in the aglycone side chain, demonstrate rather strong hemolytic and cytotoxic activities.

A new triterpene glycoside cucumarioside I2 (1) has been isolated from holothurian Eupentacta fraudatrix. The structure of 1 was elucidated using extensive NMR spectroscopy ((1)H and (13)C NMR, (1)H-(1)H COSY, 1D TOCSY, HSQC, H2BC, HMBC and NOESY) and MALDI-TOF-MS. Glycoside 1 is a disulfated branched pentaoside having rare 3-O-methyl-D-xylose. Cytotoxic activity of the glycoside 1 and known cucumariosides H (2), A5 (3), A6 (4), B2 (5) and B1 (6) against mouse Ehrlich carcinoma cells and their influence on lysosomal activity of mouse peritoneal macrophages have been studied. Glycosides 1 and 5 possessed low cytotoxicities, glycoside 6 was not cytotoxic while compounds 2, 3 and 4 possessed moderate cytotoxicities. Glycosides 1, 3 and 5 increased the lysosomal activity of macrophages on 15-17% at doses of 1-5 μg/mL. Hence lysosomal activity depends on structures of both aglycone and carbohydrate chain and does not have a direct correlation with cytotoxicities of the glycosides.

Two new minor triterpene glycosides, cucumariosides B1 (1) and B2 (2) have been isolated from the Far Eastern sea cucumber Eupentacta fraudatrix. Structures of the glycosides were elucidated by 2D NMR spectroscopy and MS. Glycosides 1 and 2 belong to the cucumariosides B group and have unprecedented trisaccharide carbohydrate moieties without sulfate groups. Glycosides 1 and 2 differ from each other in side chain structures in the aglycone moieties. These minor substances are probably intermediate metabolites in the biosynthesis of triterpene pentaosides. Cytotoxic activities of glycosides 1 and 2 against mouse spleen lymphocytes and the cells of the ascite form of mouse Ehrlich carcinoma were studied, along with hemolytic activity against mouse erythrocytes and antifungal activity. Cucumarioside B1 (1) was not active in any of the tests, while cucumarioside B2 (2) demonstrated moderate hemolytic activity and low cytotoxic action against Ehrlich carcinoma cells.

Seven new minor triterpene glycosides, cucumariosides A2 (1), A7 (2), A9 (3), A10 (4), A11 (5), A13 (6) and A14 (7) have been isolated from the Far Eastern sea cucumber Eupentacta fraudatrix. Structures of the glycosides were elucidated by 2D NMR spectroscopy and MS. Glycosides 1-7 belong to the group of cucumariosides A, having linear tetrasaccharide carbohydrate moieties without any sulfate group and possessing 3-O-methyl-D-xylose as a terminal monosaccharide unit. Glycosides 1, 2, 5-7 differ from each other in side chain structures in aglycone moieties, while cucumarioside A10 (4) has a 23,24,25,26,27-pentanorlanostane aglycone with 18(16)-lactone. Cucumarioside A9 (3), having an uncommon 18-hydroxy group, is the second representative of the unique metabolically active glycosides that are regarded as intermediates of glycoside biosynthesis in sea cucumbers. Cytotoxic activities of glycosides 1-7 and cucumarioside A8 (8) against mouse spleen lymphocytes and the cells of the ascite form of mouse Ehrlich carcinoma, along with hemolytic activity against mouse erythrocytes and antifungal activity were studied. Cucumariosides A2 (1), A8 (8) and A13 (6) demonstrated high hemolytic activities. Glycosides 1, 4 and 6 showed moderate cytotoxic activity. Only cucumarioside A8 (8), having an 18-oxymethylene group and a 24(25)-double bond, was very active in all the tests.

Seven new minor triterpene glycosides, cucumariosides A1 (1), A3 (2), A4 (3), A5 (4), A6 (5), A12 (6) and A15 (7) have been isolated from the Far Eastern sea cucumber Eupentacta fraudatrix. Structures of the glycosides were elucidated by 2D NMR spectroscopy and MS. Glycosides 1-7 belong to the group of cucumariosides A, having linear tetrasaccharide carbohydrate moieties without any sulfate group and possessing 3-O-methyl-D-xylose as a terminal monosaccharide unit. The latter peculiarity is rare in sea cucumber glycosides, but typical for the glycosides from E. fraudatrix. Glycosides 1-7 differ from each other by side chain structures in the aglycone moieties; three of them have unique structural features. The first is the presence of a 25-butoxy-group in the side chain of cucumarioside A3 (2), the second is a 23E,25-diene system in cucumarioside A6 (5) and the third is a 25-keto-27-nor-holostane aglycone in cucumarioside A12 (6); these were never previously found in sea cucumber glycosides. Cytotoxic activity of glycosides 1-7 against mouse spleen lymphocytes and the cells of the ascite form of mouse Ehrlich carcinoma, along with hemolytic activity against mouse erythrocytes and antifungal activity were studied. Glycosides 1 and 5 were the most active in all the tests.

New triterpene glycosides, cucumariosides H₂ (1), H₃ (2) and H₄ (3), have been isolated from the Far Eastern sea cucumber Eupentacta fraudatrix. The structures of 1-3 were elucidated using extensive NMR spectroscopy (¹H- and ¹³C-NMR, DEPT, ¹H-¹H COSY, 1D TOCSY, H2BC, HMBC, heteronuclear single-quantum coherence, and NOESY) and ESI-MS. Glycosides 1-3 are monosulphated branched pentaosides having rare 3-O-methyl-D-xylose as a terminal monosaccharide. Glycosides 1 and 3 contain holostane aglycones, whereas 2 has a 23,24,25,26,27-pentanorlanostane aglycone with an 18(16)-lactone, which is also uncommon for the sea cucumbers. Glycoside 3 contains a very rare ethoxyl radical at C-25 of the aglycone side chain, and it is most probably an artefact that was formed during long storage of the ethanolic extract. Cytotoxic activities of 1-3 against mouse spleen lymphocytes, haemolytic activity against mouse erythrocytes and Ehrlich carcinoma cells have been studied. The presence of 25-hydroxy group in aglycone moiety significantly decreased the activities.

Four new triterpene glycosides cucumariosides H5 (1), H6 (2), H7 (3) and H8 (4) along with the known cucumarioside H (5) have been isolated from the Far Eastern sea cucumber Eupentacta fraudatrix. The structures of glycosides 1-4 were elucidated on the basis of spectral data (2D NMR and MS). Glycosides 1-4 belong to the group o f cucumariosides H having branched rare pentasaccharidecarbohydrate moieties with one sulfate group and 3-O-methyl-D-xylose as a terminal monosaccharide unit. Glycosides 1-3 and 5 differ from each other in structures of side chains of the aglycones, while cucumarioside H8 (4) has a novel aglycone with unprecedented 16(22)-epoxy-group, never found in the sea cucumbers glycosides. Glycosides 1-3, and 5 were cytotoxic against mouse lymphocytes and hemolytic against mouse erythrocytes. Glycoside 2 was less active in comparison with others.