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

Five new triterpene di-, tri- and tetrasulfated hexaosides (chitonoidosides I (<b>1</b>), J (<b>2</b>), K (<b>3</b>), K₁ (<b>4</b>) and L (<b>5</b>)) were isolated from the Far-Eastern sea cucumber <i>Psolus chitonoides</i>, 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 <b>1</b>–<b>5</b> against human erythrocytes as well as cytotoxicity against human cancer cell lines, HeLa, DLD-1 and HL-60, were studied. The hexaosides, chitonoidosides K (<b>3</b>) and L (<b>5</b>) 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 <b>5</b> as compared with <b>3</b>, 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 <b>1</b> and <b>2</b> demonstrated some weaker action in relation to DLD-1 cells than against other tumor cell lines. Chitonoidoside K₁ (<b>4</b>) 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 <i>P. chitonoides</i> as well as the aglycones biosynthetic transformations during their biosynthesis are discussed and illustrated with schemes.