Nine New Triterpene Glycosides, Magnumosides A1-A4, B1, B2, C1, C2 and C4, from the Vietnamese Sea Cucumber Neothyonidium (=Massinium) magnum: Structures and Activities against Tumor Cells Independently and in Synergy with Radioactive Irradiation

Nine new sulfated triterpene glycosides, magnumosides A(1) (1), A(2) (2), A(3) (3), A(4) (4), B-1 (5), B-2 (6), C-1 (7), C-2 (8) and C-4 (9) as well as a known colochiroside B-2 (10) have been isolated from the tropical Indo-West Pacific sea cucumber Neothynidium (=Massinium) magnum (Phyllophoridae, Dendrochirotida) collected in the Vietnamese shallow waters. The structures of new glycosides were elucidated by 2D NMR spectroscopy and mass-spectrometry. All the isolated new glycosides were characterized by the non-holostane type lanostane aglycones having 18(16)-lactone and 7(8)-double bond and differed from each other by the side chains and carbohydrate moieties structures. Magnumoside A(1) (1) has unprecedented 20(24)-epoxy-group in the aglycone side chain. Magnumosides of the group A (1-4) contained disaccharide monosulfated carbohydrate moieties, of the group B (5, 6)-tetrasaccharide monosulfated carbohydrate moieties and, finally, of the group C (7-9)-tetrasaccharide disulfated carbohydrate moieties. The cytotoxic activities of the compounds 1-9 against mouse spleen lymphocytes, the ascites form of mouse Ehrlich carcinoma cells, human colorectal carcinoma DLD-1 cells as well as their hemolytic effects have been studied. Interestingly, the erythrocytes were more sensitive to the glycosides action than spleenocytes and cancer cells tested. The compounds 3 and 7 significantly inhibited the colony formation and decreased the size of colonies of DLD-1 cancer cells at non-cytotoxic concentrations. Moreover, the synergism of effects of radioactive irradiation and compounds 3 and 7-9 at subtoxic doses on proliferation of DLD-1 cells was demonstrated.