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

Abstract

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.