Pelageya V. Andryjaschenko

Structures and cytotoxic properties of cucumariosides H2, H3 and H4 from the sea cucumber Eupentacta fraudatrix

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.

Structure of cucumarioside I2 from the sea cucumber Eupentacta fraudatrix (Djakonov et Baranova) and cytotoxic and immunostimulatory activities of this saponin and relative compounds

A new triterpene glycoside cucumarioside I2 (1) has been isolated from holothurian Eupentacta fraudatrix. The structure of 1 was elucidated using extensive NMR spectroscopy (1H and 13C NMR, 1H–1H 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.

Structures and biological activities of cladolosides C3, E1, E2, F1, F2, G, H1 and H2, eight triterpene glycosides from the sea cucumber Cladolabes schmeltzii with one known and four new carbohydrate chains

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.

Structures and Biogenesis of Fallaxosides D4, D5, D6 and D7, Trisulfated Non-Holostane Triterpene Glycosides from the Sea Cucumber Cucumaria fallax

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.

Structures of eremophilane-type sesquiterpene glucosides, alticolosides A-G, from the Far Eastern endemic Ligularia alticola Worosch

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.

Cladolosides I1, I2, J1, K1, K2 and L1, monosulfated triterpene glycosides with new carbohydrate chains from the sea cucumber Cladolabes schmeltzii

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.

Cladolosides O, P, P1-P3 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), P1 (3), P2 (4), P3 (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 P1 (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 P2 (4) and P3 (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.