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

Abstract

Nine new sulfated triterpene glycosides, magnumosides A1 (1), A2 (2), A3 (3), A4 (4), B1 (5), B2 (6), C1 (7), C2 (8) and C4 (9) as well as a known colochiroside B2 (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 A1 (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.

Metabolite Profiling of Triterpene Glycosides of the Far Eastern Sea Cucumber Eupentacta fraudatrix and Their Distribution in Various Body Components Using LC-ESI QTOF-MS

“…A representative example of such changes has been reported for the components of the glycosidic fraction of Psolus fabricii , where two different glycosides were predominant or minor in the samples collected near Onekotan Island or Ushishir Islands (Kuril Islands) [41,42]. Another example is given by the glycosides of Massinium (= Neothynidium ) magnum where the structures of glycosides from various places or various times of collection were strongly different [43]. In addition, some earlier isolated cucumariosides of A-group may be artifacts formed during the isolation process [24].…”

Psolusosides C1, C2, and D1, Novel Triterpene Hexaosides from the Sea CucumberPsolus fabricii (Psolidae, Dendrochirotida)

“…13 C and H NMR chemical shifts, HMBC and ROESY correlations of aglycone moiety of psolusoside C 2(2).…”

Magnumosides B3, B4 and C3, Mono- and Disulfated Triterpene Tetraosides from the Vietnamese Sea Cucumber Neothyonidium (= Massinium) magnum

“…It was found that magnumoside B 4 (2) at nontoxic dose (10 µM) decreased the number and size of colonies of DLD-1 cells by 67% and 81%, respectively (Figures 2A, B). The magnumoside B 3 (1) and magnumoside C 3 (3) inhibited spontaneous colony formation by 18% and 9%, respectively, ( Fig 2A) and, at the same time, they slightly reduced colonies size of DLD-1 cancer cells by 8% and 4%, respectively, ( Figure 2B). The synergism of radiation and the compounds effects on proliferation and colony formation of human colorectal adenocarcinoma cells has been studied.…”

“…The 1 H and 13 C NMR spectra of carbohydrate parts of magnumosides B 3 (1) and B 4 (2) were coincident to each other and to those of magnumosides B 1 and B 2 indicating the identity of carbohydrate chains of these glycosides [1]. The presence of four characteristic doublets at  H 4.65-5.21 (J = 7.3-8.0 Hz) in the 1 H NMR spectra of the carbohydrate chains of 1, 2 correlated by the HSQC spectra with the signals of anomeric carbons at  C 104.…”