A new sulfated triterpene glycoside from the sea cucumber Colochirus quadrangularis, and evaluation of its antifungal, antitumor and immunomodulatory activities.

Our continuing search for marine bioactive secondary metabolites led to the screening of crude extracts of sea cucumbers by the model of Pyricularia oryzae. A new sulfated triterpene glycoside, coloquadranoside A (1), together with four known triterpene glycosides, philinopside A, B, E and pentactaside B (2-5) were isolated from the sea cucumber Colochirus quadrangularis, and their structures were elucidated using extensive spectroscope analysis (ESI-MS, 1D and 2D NMR) and chemical methods. Coloquadranoside A possesses a 16-acetyloxy group in the holostane-type triterpene aglycone with a 7(8)-double bond, a double bond (25,26) at its side chain, and two ß-d-xylose in the carbohydrate chain. Coloquadranoside A exhibits in vitro some antifungus, considerable cytotoxicity (IC50 of 0.46-2.03 µM) against eight human tumor cell lines, in vivo antitumor, and immunomodulatory activity.

Chemistry and Bioactivity of Briaranes from the South China Sea Gorgonian Dichotella gemmacea.

Seven new briarane diterpenoids, gemmacolides AZ-BF (1-7), were isolated together with eight known analogues (8-15) from the South China gorgonian Dichotella gemmacea. Their structures were elucidated based on detailed spectroscopic analysis and a comparison with reported data. In an in vitro bioassay, these compounds exhibited different levels of growth inhibition activity against A549 and MG63 cells, giving continuous evidences about the biological contribution of functional groups at C-2, C-12, C-13, and C-16. These compounds were also evaluated for their antibacterial and antifungal activities. Compound 8 exhibited a potential antibacterial activity against both Gram-positive bacterium Bacillus megaterium and Gram-negative bacterium Escherichia coli.

Cytotoxic and apoptosis-inducing activity of triterpene glycosides from Holothuria scabra and Cucumaria frondosa against HepG2 cells.

The cytotoxic effects of thirteen triterpene glycosides from Holothuria scabra Jaeger and Cucumaria frondosa Gunnerus (Holothuroidea) against four human cell lines were detected and their cytotoxicity-structure relationships were established. The apoptosis-inducing activity of a more potent glycoside echinoside A (1) in HepG2 cells was further investigated by determining its effect on the morphology, mitochondrial transmembrane potential (Δψm) and mRNA expression levels of the apoptosis-related genes. The results showed that the number of glycosyl residues in sugar chains and the side chain of aglycone could affect their cytotoxicity towards tumor cells and selective cytotoxicity. 1 significantly inhibited cell viability and induced apoptosis in HepG2 cells. 1 also markedly decreased the Δψm and Bcl-2/Bax mRNA express ratio, and up-regulated the mRNA expression levels of Caspase-3, Caspase-8 and Caspase-9 in HepG2 cells. Therefore, 1 induced apoptosis in HepG2 cells through both intrinsic and extrinsic pathway. These findings could potentially promote the usage of these glycosides as leading compounds for developing new antitumor drugs.

Variegatusides: new non-sulphated triterpene glycosides from the sea cucumber Stichopus variegates semper.

Four new triterpene glycosides, variegatusides C-F (1-4), together with three structurally known triterpene glycosides, variegatusides A and B (5, 6), and holothurin B (7), were isolated from the sea cucumber Stichopus variegates Semper (Holothuriidae), collected from the South China Sea. Their structures were elucidated on the basis of extensive spectral analysis (nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESIMS)) and chemical evidence. Variegatusides C-F exhibit the same structural feature consisting of the presence of a 23-hydroxyl group at the holostane-type triterpene aglycone side chain. Variegatuside C (1) has a double bond (24, 25) in this same chain, while variegatuside D (2) exhibits a 8(9)-ene bond in the holostane-type triterpene aglycone, which has not been extracted from other sea cucumber species. Compound 4 is a native compound from the sea cucumber S. variegates Semper, which has been reported to be desacetylstichloroside B1. Except for holothurin B, these glycosides have no sulfate group in their sugar chain and show potent antifungal activities in vitro biotests.

New hippolide derivatives with protein tyrosine phosphatase 1B inhibitory activity from the marine sponge Hippospongia lachne.

Five new sesterterpenoids, compounds 1-5, have been isolated from the sponge Hippospongia lachne off Yongxing Island in the South China Sea. The structures of compounds 1-5 were elucidated through extensive spectroscopic analysis, including HRMS, 1D, and 2D NMR experiments. The stereochemistry, including absolute configurations of these compounds, was determined by spectroscopic, chemical, and computational methods. Compounds 1 and 5 showed moderate protein tyrosine phosphatase 1B (PTP1B) inhibitory activities with IC50 values of 5.2 µM and 8.7 µM, respectively, more potent than previously reported hippolides.

Structural and stereochemical studies of hydroxyanthraquinone derivatives from the endophytic fungus Coniothyrium sp.

Four known hydroxyanthraquinones (1-4) together with four new derivatives having a tetralone moiety, namely coniothyrinones A-D (5-8), were isolated from the culture of Coniothyrium sp., an endophytic fungus isolated from Salsola oppostifolia from Gomera in the Canary Islands. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configurations of coniothyrinones A (5), B (6), and D (8) were determined by TDDFT calculations of CD spectra, allowing the determination of the absolute configuration of coniothyrinone C (7) as well. Coniothyrinones A (5), B (6), and D (8) could be used as ECD reference compounds in the determination of absolute configuration for related tetralone derivatives. This is the first report of anthraquinones and derivatives from an isolate of the genus Coniothyrium sp. These compounds showed inhibitory effects against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium.

Bioactive polyoxygenated steroids from the South China sea soft coral, Sarcophyton sp.

Seven new polyoxygenated steroids (1-7) were isolated together with seven known analogues (8-14) from the South China Sea soft coral, Sarcophyton sp. The structures of the new compounds were identified on the basis of extensive spectroscopic analysis and comparison with reported data. All the steroids are characterized with 3ß,5α,6ß-hydroxy moiety, displaying carbon skeletons of cholestane, ergostane, gorgostane and 23,24-dimethyl cholestane. In the in vitro bioassay, metabolites exhibited different levels of antimicrobial activity against bacterial species Escherichia coli and Bacillus megaterium, and fungal species Microbotryum violaceum and Septoria tritici. No inhibition was detected towards microalga Chlorella fusca. Preliminary structure-activity analysis suggests that the 11α-acetoxy group may increase both antibacterial and antifungal activities. The terminal-double bond and the cyclopropane moiety at the side chain may also contribute to the bioactivity.

Chemistry and tumor cell growth inhibitory activity of 11,20-epoxy-3Z,5(6)E-diene briaranes from the South China Sea gorgonian Dichotella gemmacea.

Eighteen new 11,20-epoxy-3Z,5E-dien briaranes, gemmacolides AA-AR (1-18), were isolated together with three known analogs, dichotellides F (19) and I (20), and juncenolide C (21), from the South China Sea gorgonian Dichotella gemmacea. The structures of the compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configuration was determined based on the ECD experiment. In the in vitro bioassay, compounds 1-3, 5, 6, 8-12, and 14-19 exhibited different levels of growth inhibition activity against A549 and MG63 cell lines. Preliminary structure-activity analysis suggests that 12-O-isovalerate may increase the activity whereas 13- or 14-O-isovalerate may decrease the activity. Contribution of substitutions at C-2 and C-16 remains uncertain.

Bioactive briarane diterpenoids from the South China Sea gorgonian Dichotella gemmacea.

Six new briarane diterpenoids, gemmacolides T-Y (1-6), were isolated together with three known analogs, juncenolide J (7), praelolide (8), and junceellolide C (9), from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configuration was suggested based on biosynthetic considerations. In an in vitro bioassay, compounds 3 and 6 showed potent growth inhibition towards tumor cell lines of A549 and MG63, being stronger than the positive control of adriamycin. These compounds also exhibited weak antimicrobial activity against the bacterium Escherichia coli and the fungi Microbotryum violaceum and Septoria tritici.

Sinularosides A and B, bioactive 9,11-secosteroidal glycosides from the South China Sea soft coral Sinularia humilis Ofwegen.

Two new 9,11-secosteroidal glycosides, namely, sinularosides A and B (1, 2), together with the known pregnene glycoside 3ß-(ß-xylopyranosyloxy)-5α-pregna-20-ene (3), were isolated from the South China Sea soft coral Sinularia humilis Ofwegen. The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. This is the first report of 9,11-secosteroidal glycosides from a soft coral and from nature. In in vitro bioassays, the new compounds exhibited potent antimicrobial activities and showed no growth inhibition activity against the tumor cells HepG2 and Caco-2.

New bioactive sulfated alkenes from the sea cucumber Apostichopus japonicus.

Two new alkene sulfates, (5Z)-dec-5-en-1-yl sulfate (4) and (3E)-dec-3-en-1-yl sulfate (5), together with three known sulfated alkanes, 2,6-dimethylheptyl sulfate (1), octyl sulfate (2), and decyl sulfate (3), were isolated from the sea cucumber Apostichopus japonicus. The structures of the new compounds 4 and 5 were elucidated by spectroscopic analysis, including ¹H-, ¹³C-, and 2D-NMR, ESI-MS, and HR-ESI-MS. Compounds 2 and 3 were isolated from natural sources for the first time. In preliminary bioassays in vitro, compounds 4 and 5 showed antibacterial, antifungal, and cytotoxic activities.

Bioactive nonanolide derivatives isolated from the endophytic fungus Cytospora sp.

Cytospolides F-Q (6-17) and decytospolides A and B (18 and 19), 14 unusual nonanolide derivatives, were isolated from Cytospora sp., an endophytic fungus from Ilex canariensis. The structures were elucidated by means of detailed spectroscopic analysis, chemical interconversion, and X-ray single crystal diffraction. The solution- and solid-state conformers were compared by the combination of experimental methods (X-ray, NMR) supported by DFT calculations of the conformers. Absolute configurations were assigned using the modified Mosher's method and solution- and solid-state TDDFT ECD calculations. In an in vitro cytotoxicity assay toward the tumor cell lines of A549, HCT116, QGY, A375, and U973, the γ-lactone 17 demonstrated a potent growth inhibitory activity toward the cell line A-549, while nonanolide 16 with (2S) configuration showed the strongest activity against cell lines A-549, QGY, and U973. A cell cycle analysis indicated that compound 16 can significantly mediate G1 arrest in A549 tumor cells, confirming the important role of the C-2 methyl in the growth inhibition toward the tumor line. The discovery of an array of new nonanolides demonstrates the productivity of the fungus, and it is an example of chemical diversity, extending the nonanolide family by derivatives formed by ring cleavage, oxidation, esterification, and Michael addition.

Hippolides A-H, acyclic manoalide derivatives from the marine sponge Hippospongia lachne.

Eight new acyclic manoalide-related sesterterpenes, hippolides A-H (1-8), together with two known manoalide derivatives, (6E)-neomanoalide (9) and (6Z)-neomanoalide (10), were isolated from the South China Sea sponge Hippospongia lachne. The absolute configurations of 1-8 were established by the modified Mosher's method and CD data. Compound 1 exhibited cytotoxicity against A549, HeLa, and HCT-116 cell lines with IC50 values of 5.22×10(-2), 4.80×10(-2), and 9.78 µM, respectively. Compound 1 also showed moderate PTP1B inhibitory activitiy with an IC50 value of 23.81 µM, and compound 2 showed moderate cytotoxicity against the HCT-116 cell line and PTP1B inhibitory activity with IC50 values of 35.13 and 39.67 µM, respectively. In addition, compounds 1 and 5 showed weak anti-inflammatory activity, with IC50 values of 61.97 and 40.35 µM for PKCγ and PKCα, respectively.

Bioactive 11,20-epoxy-3,5(16)-diene briarane diterpenoids from the South China Sea gorgonian Dichotella gemmacea.

Seven new briarane diterpenoids, gemmacolides G-M (1-7), were isolated together with two known analogues, juncin O and junceellolide C, from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by detailed analysis of spectroscopic data and comparison with reported data. In an in vitro bioassay, these compounds exhibited different levels of growth inhibition activity against A549 and MG63 cells. In particular, compound 4 was more active than the positive control adriamycin against A549 cells. Compounds 4 and 7 also exhibited weak antimicrobial activity against the bacterium Bacillus megaterium and the fungus Septoria tritici, respectively.

Bioactive (3Z,5E)-11,20-epoxybriara-3,5-dien-7,18-olide diterpenoids from the South China Sea gorgonian Dichotella gemmacea.

Six new (3Z,5E)-11,20-epoxybriara-3,5-dien-7,18-olide diterpenoids, gemmacolides N-S (1-6), were isolated together with four known analogues, juncenolide D, and juncins R, S and U (7-10), from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by the detailed analysis of spectroscopic data in combination with the comparison with reported data. The absolute configuration of 1 was determined by a TDDFT calculation of its solution ECD spectrum, affording the determination of absolute configuration of other analogues by simply comparing their ECD spectra with that of 1. The cytotoxic and antimicrobial activities of these compounds were evaluated. In preliminary in vitro bioassays, compounds 4, 5, 6, 8 and 9 showed cytotoxicity against A549 and MG63, while compounds 1, 2, 4, 7-10 showed antimicrobial activity against the fungus Septoria tritici and the bacterium Escherichia coli.

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.

[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.

Proline-containing cyclopeptides from the marine sponge Phakellia fusca.

Four new cyclopeptides, phakellistatins 15-18 (2-5), together with five known cyclopeptides, phakellistatin 13 (1), hymenistatin 1, and hymenamides G, H, and J, were isolated from the South China Sea sponge Phakellia fusca. Their structures were elucidated by HR-ESIMS, NMR, and MALDI-TOF/TOF sequence analysis. The absolute configurations of the amino acid residues of 2-5 were assigned to be l by enantioselective HPLC analysis.

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 disulfated holostane glycosides from the sea cucumber Pentacta quadrangularis.

Two new disulfated triterpene glycosides, pentactasides B and C (1 and 2, resp.), were isolated from the sea cucumber Pentacta quadrangularis collected from the South China Sea. Their structures were elucidated by extensive spectral analysis (2D-NMR and MS) and chemical methods. The compounds 1 and 2 possess the same tetrasaccharide moieties with two sulfated groups, but are different in the side chains of the triterpene aglycone. Pentactasides B and C (1 and 2, resp.) showed significant cytotoxicities (IC(50) 0.09-2.30 microM) against different human tumor cell lines.