Cladolosides C4, D1, D2, M, M1, M2, N and Q, new triterpene glycosides with diverse carbohydrate chains from sea cucumber Cladolabes schmeltzii. An uncommon 20,21,22,23,24,25,26,27-okta-nor-lanostane aglycone. The synergism of inhibitory action of non-toxic dose of the glycosides and radioactive irradiation on colony formation of HT-29 cancer cells

Abstract

Eight new triterpene olygoglycosides, cladolosides C₄ (1), D₁ (2), D₂ (3), M (4), M₁ (5), M₂ (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 C₄ (1) contains an uncommon 20,21,22,23,24,25,26,27-octa-norlanostane aglycone. Cladolosides D₁ (2), D₂ (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 D₂ (3), inhibited the colony formation and growth of HT-29 cells at non-cytotoxic concentrations. The highest inhibitory activity was demonstrated by cladoloside M₁ (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.

Keywords: Biosynthetic pathways; Carbohydrate chains; Cladolabes schmeltzii; Cytotoxic activity; NMR; Radioactive irradiation; Triterpene glycosides.