New holostan-type triterpene glycosides from the sea cucumber Apostichopus japonicus.

Two new holostan-type glycosides, holotoxin D1 (1) and 25,26-dihydroxy-holotoxin A1 (2), together with two known analogues, stichlorosides C1 (3) and bivittoside D (4), were isolated from the sea cucumber Apostichopus japonicus Selenka. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis. Glycosides 1 and 3 exhibited potent antifungal activity.

Synthesis of novel derivatives of esculentoside A and its aglycone phytolaccagenin, and evaluation of their haemolytic activity and inhibition of lipopolysaccharide-induced nitric oxide production.

A series of 46 compounds derived from esculentoside A and its aglycone were synthesized and characterized. The effect of these compounds on lipopolysaccharide (LPS)-induced NO production, haemolytic activity, and cell viability was evaluated. Structure-activity relationship was established by comparing the derivatives of esculentoside A with its aglycone derivatives. Both the aglycone and its derivatives showed higher inhibitory effects on LPS-induced NO production, and lower haemolytic activities than esculentoside A and its derivatives.

Bioactive aromatic derivatives from endophytic fungus, Cytospora sp.

Two new benzyl gamma-butyrolactone analogues, (R)-5-((S)-hydroxy(phenyl)-methyl)dihydrofuran-2(3H)-one (1) and its 6-acetate (2), and a new naphthalenone derivative (8), together with eight additional known aromatic derivatives, (S)-5-((S)-hydroxy(phenyl)-methyl)dihydrofuran-2(3H)-one (3), (S)-5-benzyl-dihydrofuran-2(3H)-one (4), 5-phenyl-4-oxopentanoic acid (5), gamma-oxo-benzenepentanoic acid methyl ester (6), 3-(2,5-dihydro-4-hydroxy-5-oxo-3-phenyl-2-furyl)propionic acid (7), (3R)-5-methylmellein (9), integracins A (10) and B (11) were isolated from Cytospora sp., an endophytic fungus isolated from Ilex canariensis from Gomera. The structures of these compounds were elucidated by detailed spectroscopic analysis, comparison with reported data, and chemical interconversion. The absolute configurations of the new compounds (1, 2, 8) were established on the basis of optical rotation or CD spectra analysis. Preliminary studies showed antimicrobial activity of these compounds against the fungi Microbotryum violaceum, Botrytis cinerea and Septoria tritici, the alga Chlorella fusca, and the bacterium Bacillus megaterium.

[Studies on antitumor activities of triterpene glycoside colochiroside A from sea cucumber Colochirus anceps].

OBJECTIVE: To study the antitumor activities of the triterpene glycoside colochiroside A (CA) from the sea cucumber Colochirus anceps. METHOD: The tests of antitumor activities in vitro and in vivo were applied to demonstrate the effect of CA. RESULT: The preliminary cytotoxic assay of CA exhibited significant cytotoxic activity against 6 types cultured tumor cell lines of p388, HL60, A-549, SpC-A4, MKN-28, and SGC-7901, the mean of IC50 were (3.61 +/- 0.55) mg x L(-1). The preliminary antitumor assay of CA indicated that this saponin exhibited high inhibiting activity against the H22 live cancer and the S180 sarcoma cells in mouse. The inhibition ratio to H22 liver cancer were 34.8%, 43.9% and 52.2%, while the ratio to S180 sarcoma were 36.4%, 70.0%, the immunoregulatory founction study indicated CA has not significant effect on the developments of thymus and spleen. CONCLUSION: The saponin CA exhibited remarkable antineoplastic activities in vitro and in vivo, and could not reduce the immunoregulatory founction of mice.

Cytotoxic holostane-type triterpene glycosides from the sea cucumber Pentacta quadrangularis.

Two new holostane-type triterpene glycosides, named pentactasides I (1) and II (2), and a new natural product, pentactaside III (3), together with two known glycosides, philinopsides A (4) and B (5), were isolated from the sea cucumber Pentacta quadrangularis. Their structures were elucidated by extensive spectroscopic analysis and chemical evidences. Compounds 1 and 2 possess the same trisaccharide moiety which is a rare structural feature among naturally occurring sea cucumber glycosides and has been infrequently reported, while 3 is a sulfated diglycoside. All the glycosides showed significant in vitro cytotoxicities against six tumor cell lines (P-388, A-549, MCF-7, MKN-28, HCT-116, and U87MG) with IC(50) in the range of 0.60-3.95 µM.

Two new cytotoxic triterpene glycosides from the sea cucumber Holothuria scabra.

Two new triterpene glycosides, scabraside A (1) and B (2), and a structurally known compound (3), were isolated from the sea cucumber Holothuria scabra (Holothuriidae) collected from the South China Sea. Structure of these compounds was elucidated by spectroscopic and chemical methods. The glycosides 1 and 2 exhibit the same common structural features, i. e., the presence of 12- and 17-hydroxy groups in the holostane-type triterpene aglycone with a 9(11)-ene bond, but are different in the side chains of the triterpene aglycone. The glycosides 1 and 2 had significant in vitro cytotoxicity against four human tumor cell lines in comparison to 10-hydroxycamptothecin.

Antifungal triterpene glycosides from the sea cucumber Holothuria (Microthele) axiloga.

Three new holostan-type triterpene glycosides, arguside F (1), impatienside B (2), and pervicoside D (3), together with a known saponin, holothurin B ( 4) were isolated from the sea cucumber Holothuria (Microthele) axiloga H. L. Clark. On the basis of spectroscopic data and chemical reactions, the structures of the new compounds were elucidated. Compound 2 showed significant antifungal activities against six strains (1 < or = MIC(80) < or = 4 microg/mL). The stereochemistry of holothurin B (4) isolated from the title sea cucumber was also solved through X-ray diffraction analysis.

Antifungal triterpene glycosides from the sea cucumber Bohadschia marmorata.

Four new holostan-type triterpene glycosides, marmoratoside A ( 1), 17 alpha-hydroxy impatienside A ( 2), marmoratoside B ( 3), 25-acetoxy bivittoside D ( 4), together with two known triterpene glycosides, impatienside A ( 5) and bivittoside D ( 6), were isolated from the sea cucumber Bohadschia Marmorata Jaeger. On the basis of spectroscopic analyses, including two-dimensional NMR techniques, and chemical reactions, the structures of the new triterpene glycosides were elucidated. Compounds 1, 2, 5, and 6 exhibited significant antifungal activity against six strains (0.70 < or = MIC (80) < or = 2.81 microM).

Cytotoxic triterpene glycosides from the sea cucumber Pseudocolochirus violaceus.

A new triterpene glycoside (1) along with the known intercedenside B (2) was isolated from the sea cucumber Pseudocolochirus violaceus. Glycoside 1 was elucidated as 3-O-{6-O-sodiumsulfate-3-O-methyl-beta-D-glucopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-[beta-D-xylopyranosyl(1-->2)]-beta-D-quinovopyranosyl-(1-->2)-4-O-sodiumsulfate-beta-D-xylopyranosyl}-16beta-acetoxy-holosta-7, 24-diene-3beta-ol on the basis of extensive spectral studies and chemical evidence. Both the glycosides exhibited significant cytotoxicity against cancer cell lines MKN-45 and HCT-116.

Protective effect of esculentoside A on radiation-induced dermatitis and fibrosis.

PURPOSE: To investigate the effect of esculentoside A (EsA) on radiation-induced cutaneous and fibrovascular toxicity and its possible molecular mechanisms, both in vivo and in vitro. METHODS AND MATERIALS: Mice received drug intervention 18 hours before 30 Gy to the right hind leg. Alterations in several cytokines expressed in skin tissue 2 days after irradiation were determined by ELISA. Early skin toxicity was evaluated 3 to 4 weeks after irradiation by skin scoring, and both tissue contraction and expression of TGF-beta1 were determined for soft-tissue fibrosis 3 months after irradiation. In vitro, the effect of EsA on radiation-induced nitric oxide (NO) and cytokine production in different cell types was measured by application of 2, 4, and 8 Gy. RESULTS: In vivo, EsA reduced levels of IL-1alpha, MCP-1, VEGF, and TGF-beta1 in cutaneous tissue and reduced soft-tissue toxicity. In vitro, EsA inhibited the IL-1alpha ordinarily produced after 4 Gy in A431 cells. In Raw264.7 cells, EsA reduced levels of IL-1alpha, IL-1beta, and NO production costimulated by radiation and lipopolysaccharide (LPS). In L-929 cells, EsA inhibited VEGF, TNF, and MCP-1 production at 2, 4, and 8 Gy. CONCLUSIONS: Esculentoside A protects soft tissues against radiation toxicity through inhibiting the production of several proinflammatory cytokines and inflammatory mediators in epithelial cells, macrophages, fibroblasts, and skin tissue.

Nobilisides A - C, three new triterpene glycosides from the sea cucumber Holothuria nobilis.

Three new triterpene glycosides, named nobilisides A ( 1), B ( 2) and C ( 3), were isolated from the sea cucumber Holothuria nobilis Selenka. Their structures were deduced by extensive spectral analysis and chemical evidence. Compounds 1 and 3 are non-sulfated monoglycosides while 2 is a sulfated diglycoside. The presence of two conjugated double bonds [22 E,24-diene and 7,9(11)-diene] in the aglycone of 1 is a rare structural feature among sea cucumber glycosides, while 2 and 3 possess the same 22,25-epoxy moiety as their side chains. All three glycosides exhibited significant cytotoxicity against human tumor cell lines.

[Isolation and structural elucidation of a bioactive saponin from tubers of Bolbostemma paniculatum].

OBJECTIVE: To study the bioactive constituents from tubers of Bolbostemma paniculatum. METHOD: Compounds were isolated by extraction and partition as well as several-chromatographic techniques guided with Pyricularia oryzae bioassay method. Their structures were determined on the basis of spectral analysis and chemical evidence. RESULT: Bisdesmoside (I) was isolated as active compound causing morphological abnormality of Pyncularia oryzae mycelia and elucidated as 3-0-alpha-L-arabinopyranosyl (1-->2)-beta-D-glucopyranosyl-bayogenin-28-O-beta-D-xylopyranosyl (1-->3)-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranoside. CONCLUSION: I is a new natural product and exhibited significant cytotoxicity against cancer cell lines K-562 and BEL-7402, but no hemolytic activity to rabbit erythrocytes.

Asterosaponins from the starfish Culcita novaeguineae and their bioactivities.

Bioassay-guided fractionation of the n-BuOH extract of the starfish Culcita novaeguineae resulted in the isolation of one new sulfated steroidal glycoside (asterosaponin) (1), along with three known asterosaponins, thornasteroside A (2), marthasteroside A(1) (3) and regularoside A (4), as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. Their structures were elucidated by extensive spectral studies and chemical evidences. All the saponins showed moderate cytotoxicity against cancer cell lines K-562 and BEL-7402.

Three new asterosaponins from the starfish Culcita novaeguineae and their bioactivity.

Bioassay-guided fractionation of the active n-BuOH extract of the starfish Culcita novaeguineae resulted in the isolation of three new sulfated steroidal glycosides (asterosaponins) 1, 2 and 3, as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. Compounds 1-3 possess the same pentasaccharide moiety, beta-D-fucopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->4)-[beta-D-quinovopyranosyl-(1-->2)]-beta-D-xylopyranosyl-(1-->3)-beta-D-quinovopyranosyl, linked to C-6 of 3beta-sulfated steroidal aglycones and differ from each other in the side chains. Their structures were elucidated by extensive spectral studies and chemical evidences. Saponins 1 and 3 showed significant cytotoxicity against two cancer cell lines (IC50 values for 1:3.57 microg/mL [K-562], 2.55 microg/mL [BEL-7402]; for 3:3.75 microg/mL [K-562], 1.89 microg/mL [BEL-7402]), as well as hemolytic activity to rabbit erythrocytes (ED50 values: 16 and 31 microg/mL, respectively), while 2 was inactive in these bioassays.

[Therapeutical effects of esculentoside A on rats with MsPGN induced by anti-Thy1.1 antibody].

OBJECTIVE: To observe the therapeutical effects of esculentoside A (EsA) on rats with mesangial proliferative glomerulonephritis (MsPGN) induced by anti-Thy1.1 antibody and make a comparison of the effects between EsA and dexamethasone (DXM). METHODS: Wistar rats with MsPGN induced by anti-Thy1.1 serum (ATS) were randomly divided into 3 groups: EsA group, DXM group, and model group. Moreover, a normal group was used for comparison. The BUN, SCr, urinary protein and renal pathological changes were examined after 7 d treatment with EsA and DXM. RESULTS: The urinary protein, cell count and mesangium area of glomerulus were significantly higher in all modeled groups than in normal group (P<0.001-0.05), and they were significantly lower in the treated groups than in untreated group (P<0.001-0.01). CONCLUSION: The results suggest that EsA is effective for reducing the urinary protein excretion and inhibiting the proliferation process of glomerular mesangium and matrix in rats with MsPGN.

[The lignins from Torreya grandis cv. Merrilli].

AIM: To separate and identify the chemical constituents of the aril of Torreya grandis cv. Merrilli. METHODS: Three lignins were isolated by chromatography and their chemical structures were elucidated by IR, EI-MS, 1HNMR, 13CNMR, DEPT and 2D-NMR spectral methods. RESULTS: Three lignins were identified as pinonesinol, dihydrodehydrodiconiferylalcohol and (7,8-cis-8,8'-trans)-2',4'dihydroxyl-3, 5-dimethoxy-lariciresinol. CONCLUSION: These compounds were isolated from this plant for the first time, and compound III is a new compound.

[A new chromone glycoside from Cassia siamea lam].

AIM: To study the chemical constituents of the stem of Cassia siamea. METHODS: The compounds were isolated by chromatography on silica gel, and identified on the basis of spectral analysis. RESULTS: Five compounds were isolated and identified as: beta-sitosterol (I), sucrose (II), n-octacosanol (III), 2-methyl-5-(2'-hydroxypropyl)-7-hydroxy-chromone-2'-O-beta-D-glucopyranoside (IV) and piceatannol (V). CONCLUSION: Compound IV is a new compound. Compounds II, III and V were obtained from this plant for the first time.

Anti-AIDS agents 54. A potent anti-HIV chalcone and flavonoids from genus Desmos.

Sixteen flavonoids and their derivatives isolated from Desmos spp. were evaluated for inhibition of HIV replication in H9 lymphocyte cells. 2-Methoxy-3-methyl-4,6-dihydroxy-5-(3'-hydroxy)cinnamoylbenzaldehyde (12) and lawinal (6) demonstrated potent anti-HIV activity with EC(50) values of 0.022 and 2.30 microg/mL and therapeutic indexes of 489 and 45.2, respectively. Compound 12 appears to be an excellent lead for further anti-HIV drug development.

Effect of esculentoside A on autoimmunity in mice and its possible mechanisms.

AIM: To investigate the influence of esculentoside A (EsA) on autoimmunity in mice and its possible mechanisms. METHODS: The level of anti-ds DNA antibody, proliferation of lymphoid cells, and inflammation by pathologic section of joint in mice were examined. The autoimmunity model is made through immunizing mice with formaldehyde treated Campylobacter jejuni strain CJ-S131 and Freund's complete adjuvant. The apoptosis of T cell was analyzed through morphology and flow cytometry (FACS). The expression of ICAM-1 mRNA in human umbilical vein endothelial cell line (ECV304) was determined by coupled reverse transcription and PCR amplification (RT-PCR). RESULTS: EsA could potently lower the level of anti-ds DNA antibody, inhibit the proliferation of lymphoid cells, and ameliorate inflammation in the joint of model mouse. The apoptosis of thymocyte activated by ConA was markedly accelerated while the expression of ICAM-1 mRNA in ECV304 was decreased by EsA. CONCLUSION: EsA has the positive curative effect on autoimmunity in a mouse model, which may function through inhibition of expression of ICAM-1 mRNA in ECV304 and acceleration of thymocyte apoptosis.

[Screening of antimitotic portions from sea hare using conidia of Pyricularia Oryzae].

OBJECTIVE: To apply conidia of Pyricularia Oryzae to the screening of antimitotic constituents from marine animal sea hare. METHOD: To extract and fractionate active portions from sea hare through detecting deformation of mycelia germinated from conidia of P. Oryzae P-2b, in comparison with the cytotoxic test results in vitro. RESULT: Two active portions, of which IC50 against P388 and HL-60 was 23.4, 18.6 and 19.4, 12.5 micrograms.ml-1, respectively, were screened from this animal. CONCLUSION: This bioassay method was efficiently applied to the primary screening of antimitotic portions from marine animals for the first time. Being convenient, speedy and cheap, the screening model is suitable for the bioassay of active constituents from marine life.