Triterpene Glycosides from the Far Eastern Sea Cucumber Thyonidium (=Duasmodactyla) kurilensis (Levin): The Structures, Cytotoxicities, and Biogenesis of Kurilosides A3, D1, G, H, I, I1, J, K, and K1

Abstract

Nine new mono-, di-, and trisulfated triterpene penta- and hexaosides, kurilosides A3 (1), D1 (2), G (3), H (4), I (5), I1 (6), J (7), K (8), and K1 (9) and two desulfated derivatives, DS-kuriloside L (10), having a trisaccharide branched chain, and DS-kuriloside M (11), having hexa-nor-lanostane aglycone with a 7(8)-double bond, have been isolated from the Far-Eastern deep-water sea cucumber Thyonidium (=Duasmodactyla) kurilensis (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 16β,(20S)-dihydroxy-fragment and a 16β-acetoxy,(20S)-hydroxy fragment) were found in these glycosides. All the glycosides 1–9 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. The analysis of the structural features of the aglycones and the carbohydrate chains of all the glycosides of T. kurilensis showed their biogenetic relationships. Cytotoxic activities of the compounds 1–9 against mouse neuroblastoma Neuro 2a, normal epithelial JB-6 cells, and erythrocytes were studied. The highest cytotoxicity in the series was demonstrated by trisulfated hexaoside kuriloside H (4), having acetoxy-groups at C(16) and C(20), the latter one obviously compensated the absence of a side chain, essential for the membranolytic action of the glycosides. Kuriloside I1 (6), differing from 4 in the lacking of a terminal glucose residue in the bottom semi-chain, was slightly less active. The compounds 1–3, 5, and 8 did not demonstrate cytotoxic activity due to the presence of hydroxyl groups in their aglycones.

Unusual Structures and Cytotoxicities of Chitonoidosides A, A1, B, C, D, and E, Six Triterpene Glycosides from the Far Eastern Sea Cucumber Psolus chitonoides

“…Thus, a number of newly found sulfated hexaosides continue to grow since monosulfated hexaosides were isolated first from Cladolabes schmeltzii [25]. After that finding, di-and trisulfated compounds with hexasaccharide chains were found in T. kurilensis [9] and in P. chitonoides (chitonoidoside E (6) having two sulfate groups). We were surprised that the replacement of 18(20)-lactone for 18 (20)-epoxide in the aglycones does not significantly affect the cytotoxic activities of isolated glycosides.…”

“…The isolation of glycosides from different sea cucumber species provides a unique opportunity to expand knowledge on their structural diversity and discover new unusual substances. The comparative structural analysis of a significant number of the isolated glycosides leads to the reconstruction of the sequences of biosynthetic transformations of their aglycones and carbohydrate chains during biosynthesis that can be reflected in the metabolic networks constructed for different species of the sea cucumbers [9,10]. The studies on biological activity of the glycosides reveal the peculiarities of «structure-activity relationships» demonstrating the significance constructed for different species of the sea cucumbers [9,10].…”

“…The comparative structural analysis of a significant number of the isolated glycosides leads to the reconstruction of the sequences of biosynthetic transformations of their aglycones and carbohydrate chains during biosynthesis that can be reflected in the metabolic networks constructed for different species of the sea cucumbers [9,10]. The studies on biological activity of the glycosides reveal the peculiarities of «structure-activity relationships» demonstrating the significance constructed for different species of the sea cucumbers [9,10]. The studies on biological activity of the glycosides reveal the peculiarities of «structure-activity relationships» demonstrating the significance of different structural parts of glycosides for the realization of their physiological action.…”

Progress in the Studies of Triterpene Glycosides From Sea Cucumbers (Holothuroidea, Echinodermata) Between 2017 and 2021

“…In the completion of studies on triterpene glycosides from Thyonidium kurilensis, nine new mono-, di-, and trisulfated triterpene penta-and hexaosides, kurilosides A 3 (23), D 1 (24), G (25), H (26), I (27), I 1 (28), J (29), K (30), and K 1 (31) (Figure 6) and two desulfated derivatives, DS-kuriloside L (33), having a trisaccharide branched chain, and DS-kuriloside M (32) (Figure 7), having a hexa-nor-lanostane aglycone with a 7(8)-double bond, were isolated. 21 Structures of native glycosides and their desulfated derivatives were elucidated using 2D NMR spectroscopy and high resolution ESI mass-spectrometry. Five earlier unknown carbohydrate chains and two aglycones (having a 16β,20S-dihydroxy-fragment and a 16β-acetoxy,20S-hydroxy fragment) were found in these glycosides.…”

“…Nine new triterpene glycosides were isolated from the sea cucumber Thyonidium (=Duasmodactyla) kurilensis in addition to the series of kurilosides, found recently. 20,21 Five new types of carbohydrate chains (kurilosides of groups G-K) were discovered. There were trisulfated penta-(kurilosides of the group I [27,28]) and hexaosides {kuriloside H (26)} among them.…”