Structures and Biologic Activity of Chitonoidosides I, J, K, K1 and L-Triterpene Di-, Tri- and Tetrasulfated Hexaosides from the Sea Cucumber Psolus chitonoides

Abstract

Five new triterpene di-, tri- and tetrasulfated hexaosides (chitonoidosides I (1), J (2), K (3), K1 (4) and L (5)) were isolated from the Far-Eastern sea cucumber Psolus chitonoides, 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 1–5 against human erythrocytes as well as cytotoxicity against human cancer cell lines, HeLa, DLD-1 and HL-60, were studied. The hexaosides, chitonoidosides K (3) and L (5) with four sulfate groups, were the most active against tumor cells in all the tests. Noticeably, the sulfate group at C-4 of MeGlc6 did not decrease the membranolytic effect of 5 as compared with 3, having the sulfate group at C-6 of MeGlc6. Erythrocytes were, as usual, more sensitive to the action of the studied glycosides than cancer cells, although the sensitivity of leukemia promyeloblast HL-60 cells was higher than that of other tumor cells. The glycosides 1 and 2 demonstrated some weaker action in relation to DLD-1 cells than against other tumor cell lines. Chitonoidoside K1 (4) with a hydroxyl at C 25 of the aglycone was not active in all the tests. The metabolic network formed by the carbohydrate chains of all the glycosides isolated from P. chitonoides as well as the aglycones biosynthetic transformations during their biosynthesis are discussed and illustrated with schemes.

The Isolation, Structure Elucidation and Bioactivity Study of Chilensosides A, A1, B, C, and D, Holostane Triterpene Di-, Tri- and Tetrasulfated Pentaosides from the Sea Cucumber Paracaudina chilensis (Caudinidae, Molpadida)

“…Therefore, three of the five glycosides isolated from P. chilensis demonstrated high hemolytic and moderate cytotoxic activities against cancer cells. These data, along with the previous investigations of highly polar tri- and tetrasulfated glycosides [ 7 ], indicate the possible potential of these water-soluble compounds to be used as anticancer drugs.…”

“…The fourth sulfate group was positioned at C-6 MeGlc5 because of the deshielding of the signals of hydroxy methylene group to δ C 67.0 and δ H 4.99 (brd, J = 11.9 Hz); 4.78 (dd, J = 5.1; 11.9 Hz). Therefore, chilensoside D ( 5 ) is a new, sixth tetrasulfated glycoside found in sea cucumbers [ 7 , 44 ].…”

“…Cytotoxic activity of chilensosides A–D ( 1 – 5 ) against human cells, including erythrocytes and cancer cell lines SH-SY5Y, HeLa, DLD-1, HL-60, and THP-1, was studied. The earlier tested chitonoidoside L [ 7 ] was used as the positive control ( Table 7 ).…”

“…In fact, its structural analog chilensoside A 1 ( 2 ), with the same carbohydrate chain and aglycone without the OH-group, demonstrated high hemolytic and cytotoxic effects against all tested cell lines. Chilensoside D ( 5 ) is a tetrasulfated glycoside that itself is not the cause of activity depletion, because it is known that tetrasulfated hexaosides from P. chitonoides , chitonoidosides K and L, were significantly active [ 7 ]. The combination of sulfate group positions in 5 , especially at C-6 Glc3 and C-6 MeGlc5, probably negatively affected the activity.…”

“…Despite triterpene glycosides from sea cucumbers having a rather long history of investigations, there are some systematic groups, including the order Molpadida, comprising the studied species Paracaudina chilensis , which are poorly studied or unexplored chemically. The majority of recent research concerning the sea cucumber triterpene glycosides deals with the structure elucidation of the compounds isolated from representatives of the orders Dendrochirotida, Synallactida, and Holothuriida [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. The use of mass-spectrometry-based metabolomics for the solving of diverse chemical and biological issues concerning secondary metabolites has become very popular and has provided some significant results in the exploration of triterpene glycoside chemical diversity, their content and composition in different body parts [ 10 , 11 , 12 , 13 ], and their chemotaxonomy [ 14 , 15 ].…”