Antifouling activity of terpenoids from the corals Sinularia flexibilis and Muricella sp. against the bryozoan Bugula neritina.

Marine natural products are promising sources of green antifoulants. Here, a new compound (1) was isolated from the soft coral Sinularia flexibilis. This compound, another nine cembranoids (2-10) from S. flexibilis, and three eunicellin-type diterpenoids (11-13) from the gorgonian Muricella sp. were tested for antifouling activity against larval settlement of the bryozoan Bugula neritina. Compounds 2, 3, 4, 9, 12, and 13 exhibited significant antifouling activity, with EC50 values of 18.2, 99.7, 67.9, 35.6, 33.9, and 49.3 µM, respectively. Analysis of the structure-activity relationships suggested that the hydroxy group at C-13 in compound 4 reduced its antifouling activity.

Calix[4]arene Bridge Mononitration with tert-Butyl Nitrite: Synthesis of Bridging Chiral p-tert-Butylcalix[4]arene with a Mononitro Bridge Substituent.

To explore the reaction universality of bridge nitration, the mononitration of different p-tert-butylcalix[4]arene derivatives was executed with tert-butyl nitrite as a nitration reagent. The effects of calix[4]arene conformations, substituents on the lower rim, and reaction conditions on bridge mononitration are systematically studied. The bridge nitration of p-tert-butylcalix[4]arene derivatives in 1,3-alternate, 1,2-alternate, and partial cone conformations can be smoothly executed while that of p-tert-butylcalix[4]arene derivatives strictly regulated in a cone conformation cannot. The nitration product complexity shows a positive correlation with the bridge-hydrogen types, and the optimal bridge-mononitrated substrate is calix[4]arene with only one bridge-hydrogen type. The electron-withdrawing substituent on the lower rim is apparently beneficial for the bridge mononitration. As a result, a variety of bridging chiral p-tert-butylcalix[4]arenes with a mononitro bridge substituent have been successfully synthesized. The highest bridge-mononitrated yield can reach 27% from 1,3-alternate p-tert-butylcalix[4]arene biscrown-5 under optimal reaction conditions.

Mononitration of a Calix[4]arene Methylene Bridge: Synthesis and Preliminary Catalysis Performances of Bridging Chiral p-tert-Butylcalix[4]arenes with a Monoamino Bridge Substituent in a 1,3-Alternate Conformation.

In order to prepare bridging chiral p-tert-butylcalix[4]crown-5 with a mononitro bridge substituent in a 1,3-alternate conformation, a mononitration method of calix[4]arene bridging methylene has been first developed with tert-butyl nitrite as a nitration reagent. The effects of solvent, reaction temperature, reaction time, and nitration reagent dosage on bridge mononitration have been deeply explored to obtain an optimal nitration condition. The facile nitration presents a new key for calix[4]arene bridge derivatization. After further modification and diastereoisomeric resolution, a pair of bridging chiral p-tert-butylcalix[4]arenes with a monoamino bridge substituent were produced from the bridge-mono-nitrated calix[4]arene. Their preliminary catalysis results in the Henry reaction show good catalytic activities (up to 95% yield) and still low but obviously enhanced enantioselectivities (up to 22.3% ee from 7a, 6% ee from 1), which confirms that the structural transformation indeed improves asymmetric catalysis performances of bridging chiral calix[4]crown-5 amines in a 1,3-alternate conformation.

Longipetalol A: A Highly Modified Triterpenoid from Dichapetalum longipetalum.

Longipetalol A (1) is an unprecedented highly modified triterpenoid with a unique 1,2-seco-3-(2-oxo-phenylethyl)-17α-13,30-cyclodammarane skeleton, featuring an acetal-lactone fragment. It was isolated from Dichapetalum longipetalum along with two additional derivatives, namely, longipetalols B (2) and C (3). Their structures were elucidated using spectroscopic analyses combined with single-crystal X-ray diffraction. Compounds 1, 2, and 3 exhibited inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages.

Steroidal saponins from the rhizome of Polygonatum sibiricum.

Four new steroidal saponins, 3-O-ß-D-glucopyranosyl(1→4)-ß-D-fucopyranosyl -(25R)-spirost-5-en-3ß,17α-diol (1), 3-O-ß-D-glucopyranosyl(1→4)-ß-D- fucopyranosyl-(25S)-spirost-5-en-3ß,17α-diol (2), 3-O-ß-D-glucopyranosyl(1→2) -ß-D-glucopyranosyl(1→4)-ß-D-fucopyranosyl-(25R)-spirost-5-en-3ß,17α-diol (3), 3-O-ß-D-glucopyranosyl(1→4)-ß-D-fucopyranosyl-(25R/S)-spirost-5-en-3ß,12ß-diol (4), together with five known steroidal saponins were isolated from the ethanolic extract of the rhizome of Polygonatum sibiricum. Chemical structures of these compounds were elucidated by spectroscopic techniques. Anti-inflammatory activities of these new compounds were evaluated.

1,6-O,O-Diacetylbritannilactone suppresses activation of mast cell and airway hyper-responsiveness.

Mast cells play critical roles in allergic disorders such as atopic dermatitis and allergic asthma. The aim of this study was to investigate the anti-inflammatory and anti-asthmatic activities of 1,6-O,O-diacetylbritannilactone (OODBL) isolated from Inula japonica Thunb. (I. japonica) in a murine asthma model and bone marrow-derived mast cells (BMMCs). In an ovalbumin-induced asthma model, OODBL administration attenuated the airway hyper-responsiveness induced by aerosolized methacholine and serum IgE level in asthmatic mice. In vitro system, we found that OODBL reduced leukotriene C4 production and degranulation through the suppression of cytosolic phospholipase A2 phosphorylation and phospholipase Cγ-mediated Ca2+ influx in IgE/antigen-stimulated BMMCs. Taken together, OODBL may have therapeutic potential in the treatment of allergic diseases such as asthma.

Two new eunicellin diterpenoids from the East China Sea gorgonian Muricella sp.

A phytochemical investigation on gorgonian Muricella sp. from East China Sea resulted in the isolation of eight eunicellin diterpenoids including two new ones, muricellins A-B (1, 2). Chemical structures of these compounds were elucidated by spectroscopic techniques (1D and 2D NMR and MS) and by comparison with data reported in the literature. Anti-rheumatoid arthritis activities of 1, 3, 4, and 6 have been evaluated.

Jaspiferin G, a new isomalabaricane-type triterpenoid from the sponge Jaspis stellifera.

A new isomalabaricane-type triterpenoid, jaspiferin G (1), together with four known isomalabaricane-type triterpenoids, isogeoditin A (2), 13-(E)-isogeoditin A (3), jaspolide E (4), and 22,23-dihydrostellettin D (5), was isolated from the marine sponge Jaspis stellifera. The structures were elucidated on the basis of spectroscopic data ((1)H and (13)C NMR, (1)H(-1)H COSY, HSQC, HMBC, and ROESY) and mass spectrometry.

Three new polyunsaturated lipids from a Guangxi marine sponge Haliclona sp.

Three new polyunsaturated lipids, (6Z,9Z,12Z,15Z)-octadeca-6,9,12,15-tetraen-3-one (1), (6Z,9Z,12Z,15Z)-1-bromooctadeca-6,9,12,15-tetraen-3-one (2), and (Z)-ethyl docos-5-enoate (3), together with two known polyunsaturated lipids, 4(Z),7(Z),10(Z)-tridecatrienoic acid (4) and (6Z,9Z,12Z,15Z)-octadeca-1,6,9,12,15-pentaen-3-one (5), were isolated from the marine sponge Haliclona sp., which was collected from Guangxi, using HSCCC and HPLC methods. Chemical structures of the five compounds were elucidated by spectroscopic techniques.

[Anti-tumor metastatic constituents from Rhodiola wallichiana].

To study the anti-tumor metastatic constituents in Rhodiola wallichiana (HK) S H Fu var Cholaensis (Praeg) S H Fu, chemical constituents were isolated and purified by repeated column chromatography (silica gel, Toyopearl HW-40C and preparative HPLC). Their structures were elucidated on the basis of spectral data analysis. The anti-tumor metastasis assay was applied to evaluate the activities of the isolated compounds. Ten compounds (1-10) were isolated and their structures were identified by comparison of their spectral data with literature as follows: syringic acid (1), salidroside (2), tyrosol (3), scaphopetalone (4), berchemol (5), 2,6-dimethoxyacetophenone (6), rhobupcyanoside A (7), miyaginin (8), chavicol-4-O-ß-D-apiofuranosyl-(1 --> 6)-O-ß-D-glucopyranoside (9), eugenyol-O-ß-D-apiofuranosyl-(1 --> 6)-O-ß-D-glucopyranoside (10). Compounds 4-6 and 8-10, were isolated from this genus for the first time, while compound 7 was isolated from this plant for the first time. Compounds 2, 6-8 showed positive anti-tumor metastatic activities, and compounds 2 and 8 showed significant anti-tumor metastatic activities.

Anti-inflammatory terpenes from flowers of Inula japonica.

Five new terpenes (1-5) and ten known compounds (6-15) were isolated from Inula japonica, and their structures were identified by spectroscopic analysis. Compounds 3 and 14 showed positive inhibitory effects on nitric oxide production. Furthermore, compound 14 suppressed both leukotriene C4 synthesis and degranulation in c-kit ligand-induced bone marrow-derived mast cells.

In vitro antitumor activity of stellettin B, a triterpene from marine sponge Jaspis stellifera, on human glioblastoma cancer SF295 cells.

Stellettin B was isolated from marine sponge Jaspis stellifera. In vitro antitumor activities were investigated on 39 human cancer cell lines. Stellettin B exhibited highly potent inhibition against the growth of a human glioblastoma cell line SF295, with a GI50 of 0.01 µM. In contrast, stellettin B showed very weak inhibitory activity on normal cell lines including HMEC, RPTEC, NHBE and PrEC, with GI50s higher than 10 µM, suggesting its relatively selective cytotoxicity against human cancer cells compared to normal human cell lines. We then focused on the antitumor activity of this compound on SF295 cells. Flow cytometric analysis indicated that stellettin B induced apoptosis in SF295 cells in a concentration-dependent manner. Further study indicated that stellettin B increased the production of ROS, the activity of caspase 3/7, as well as the cleavage of PARP, each of which is known to be involved in apoptosis. To investigate the molecular mechanism for cell proliferation inhibition and apoptosis induction, effect on the phosphorylation of several signal proteins of PI3K/Akt and RAS/MAPK pathways was examined. Stellettin B inhibited the phosphorylation of Akt potently, with no activity on p-ERK and p-p38, suggesting that inhibition of PI3K/Akt pathway might be involved in the antiproliferative and apoptosis-inducing effect. However, homogenous time-resolved fluorescence (HTRF) assay indicated that stellettin B did not inhibit PI3K activity, suggesting that the direct target might be signal protein upstream of Akt pathway other than PI3K.

Antitumor metastasis pregnane alkaloids from Pachysandra terminalis.

Three new pregnane alkaloids, named terminamines H-J (1-3), together with two known alkaloids (4 and 5), were isolated from the ethanol extract of Pachysandra terminalis. The structures of isolated compounds were elucidated by spectroscopic methods, including (1)H and (13)C NMR, 2D NMR, and HR-ESI-MS. Compounds 1, 4, and 5 revealed significant anti-metastasis activities. In addition, compound 1 inhibited the expression of p-PKCζ in MDA-MB-231 cells, and compound 4 inhibited the expressions of p-PKCζ in MDA-MB-231 and A549 cells.

Jaspiferins C-F, four new isomalabaricane-type triterpenoids from the South China Sea sponge Jaspisstellifera.

A chemical investigation of marine sponge Jaspis stellifera, collected from the South China Sea, led to the isolation of four new isomalabaricane-type triterpenoids, jaspiferins C-F (1-4). The structures of those compounds were elucidated by extensive spectroscopic methods. Jaspiferin C (1), which has the six-membered carbon ring at the side chain, was discovered for the first time from the isomalabaricane-type triterpenoids. The hypothesis of a biogenetic pathway to generate jaspiferin C (1) was depicted.

Novel polyhydroxylated steroids from the East China Sea gorgonian Echinogorgia sassapo reticulata with suppressive activity of leukotriene C4 generation and degranulation in bone marrow-derived mast cells.

The gorgonian Echinogorgia sassapo reticulata contains two new bioactive polyhydroxylated steroids, sassapols A (1), B (2), and five related known compounds (3-7). Compound 6 has been encountered for the first time in natural sources. The structures of these new compounds were defined by spectroscopic analysis. All the compounds (1-7) isolated from E. sassapo reticulata were tested for anti-inflammatory activity. Compounds 1, 3, 5, and 7 inhibited both the generation of leukotriene C4 and the degranulation reaction in mouse bone marrow-derived mast cells.

[Anti-inflammatory constituents from Inula japonica].

Chemical constituents of Inula japonica were isolated and purified by repeated column chromatographies, over silica gel, and Toyopearl HW-40, and preparative HPLC. On the basis of spectral data analysis, including NMR and MS data, the structures of the isolates were elucidated and their anti-inflammatory activities were assayed. Fifteen compounds were isolated from the ethyl acetate extract of I. japonica, and their structures were elucidated as dihydrosyringenin (1), (3S, 5R, 6S, 7E)-5,6-epoxy-3-hydroxy-7-megastigmen-9-one (2), (6R, 7E) -9-hydroxy-4,7-megastigmadien-3-one (3), arnidiol (4), taraxasterol acetate (5), 8,9,10-trihydroxythymol (6), taxifolin (7), luteolin (8), napetin (9), eupatin (10), spinacetin (11), quercetin (12), p-hydroxycinnamic acid (13), caffeic acid (14), and caffeoyl acetate (15). Compounds 1, 2, 7, 13 and 15 were isolated from the genus Inula for the first time, and compounds 3, 4, 9-11 and 14 were isolated from this plant for the first time. The anti-inflammatory activity result showed that compounds 3, 6-12 and 14 exhibited inhibition effect against leukotriene C4 (LTC4) synthesis and degranulation definitely in c-Kit Ligand (KL) induced mast cells, and compound 8 and 12 also had the suppression effect against lipopolysacharide(LPS) induced nitric oxide (NO) activity in RAW264.7 macrophages. It is firstly reported that compounds 7 and 9-11 possessed potent inhibition activities against LTC4 generation and degranulation in mast cells.

Dichapetalin-type triterpenoids from Dichapetalum longipetalum and their anti-inflammatory activity.

A phytochemical research on the twigs of Dichapetalum longipetalum (Turcz.) Engl. Resulted in five undescribed dichapetalin-type triterpenoids 1-5. Their chemical structures were determined by spectroscopic analysis of HR-ESIMS and NMR spectra and the absolute configuration of compound 1 was completely elucidated by single crystal X-ray crystallography. Through preliminary anti-inflammatory activity assessment, compound 1 exhibited inhibitory effect on LPS-induced NO production in RAW264.7 murine macrophages with an IC50 value of 2.09 µM.

[Chemical constituents from Pachysandra terminalis].

To study chemical constituents from Pachysandra terminalis. By repeated column chromatography, including silica gel, Toyopearl HW-40, and preparative HPLC, four new (14) and one known (5) compounds were isolated and purified. On the basis of spectral data analysis, the structure of isolated compounds were elucidated as follow: 2-methyl-3-methylenepentane-1, 2, 5-triol (1), 4-methyl-3-methylenepentane-1, 2, 5-triol (2), 4-methyl-3-methylenepentane-1, 2, 5-triol-5-O-beta-D-glucopyranoside (3), 4-methyl-3-methylenep- entane-1, 2, 5-triol-1-O-beta-D-glucopyranoside (4), (7S, 8R, 8' R)-(+)-lariciresinol-9-O-beta-D-glucopyrano-side (5). Compound 5 was isolated from this genus for the first time.

Alkaloids from Pachysandra terminalis inhibit breast cancer invasion and have potential for development as antimetastasis therapeutic agents.

The aim of the present study was to identify potentially useful natural compounds for the development of novel therapeutic agents to inhibit metastasis. A phytochemical investigation of Pachysandra terminalis resulted in the isolation of seven new pregnane alkaloids, terminamines A-G (1-7), and seven known alkaloids (8-14). The structures of 1-7 were elucidated by 1D- and 2D-NMR spectroscopic and mass spectrometric methods. Compounds 1-5 and 8-14 inhibited the migration of MB-MDA-231 breast cancer cells induced by the chemokine epithelial growth factor. In addition, compound 1 inhibited phosphorylation of integrin ß(1), which plays an important role in MB-MDA-231 cell adhesion and metastasis.

Four new triterpenes from the endemic relict shrub Tetraena mongolica.

A chemical investigation of the endemic relict shrub Tetraena mongolica led to the isolation of four new triterpenes: 11α,12α:13ß,28-diepoxyoleanane-3ß-yl trans-caffeate (1), 3ß-hydroxy-11α,12α-epoxyoleanane-28-al (2), olean-11-en-28-al-3ß-yl trans-caffeate (3), and 28-acetoxy-olean-12-en-3ß-yl trans-caffeate (4). Their structures were elucidated by extensive spectroscopic methods.