Four new bromotryptamine derivatives from the marine bryozoan Flustra foliacea

Ten brominated alkaloids, 6-bromo-2-(1,1-dimethyl-2-propenyl)-1H-indole-3-carbaldehyde (1), N-(2-[6-bromo-2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]ethyl)-N-methylmethanesulfonamide (2), deformylflustrabromine (3), flustrabromine (4), (3aR,8aS)-6-bromo-3a-[(2E)-3,7-dimethyl-2,6-octadienyl]-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]-indol-7-ol (5), flustramine C (6), dihydroflustramine C (7), flustramine A (8), flustramine D (9), and flustraminol A (10), and the diterpene 4,6-bis(4-methylpent-3-en-1-yl)-6-methylcyclohexa-1,3-diene-carbaldehyde (11) were isolated from the dichloromethane extract of the North Sea bryozoan Flustra foliacea. Of the 10, four (1, 2, 3, and 5) represent new natural products. The structures of all isolates were elucidated by interpretation of their spectroscopic data (NMR, MS, UV, and IR). For compound 4 complete (13)C NMR data are reported for the first time. Compounds 3 and 6-8 were tested on voltage-activated potassium and sodium channels. Flustramine A (8) shows an unspecific blocking activity on Kv1.4 potassium-mediated currents.     

Bromophenols coupled with nucleoside bases and brominated tetrahydroisoquinolines from the red alga Rhodomela confervoides

Three new bromophenols C-N coupled with nucleoside base derivatives (1-3) and three new brominated 1,2,3,4-tetrahydroisoquinolines (5-7), together with a new brominated tyrosine derivative (4), have been isolated from polar fractions of an ethanolic extract of the red alga Rhodomela confervoides. By spectroscopic and chemical methods including HRMS and 2D NMR data, their structures were determined as 7-[3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyl]-3,7-dihydro-1H-purine-2,6-dione (1), 7-(2,3-dibromo-4,5-dihydroxybenzyl)-3,7-dihydro-1H-purine-2,6-dione (2), 9-[3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyl]adenine (3), (-)-8S-(3-bromo-5-hydroxy-4-methoxy)phenylalanine (4), (-)-3S-8-bromo-6-hydroxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (5), methyl (-)-3S-8-bromo-6-hydroxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (6), and methyl (-)-3S-6-bromo-8-hydroxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (7). Compounds 5-7 were semisynthesized by using 4 as the starting material.     

Bromophenol derivatives from the red alga Rhodomela confervoides

Eight new bromophenol derivatives, 2,3-dibromo-4,5-dihydroxybenzyl methyl sulfoxide (1), 4-(2,3-dibromo-4,5-dihydroxyphenyl)-3-butene-2-one (2), 2-(3-bromo-5-hydroxy-4-methoxyphenyl)-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid (3), 2-(3-bromo-5-hydroxy-4-methoxyphenyl)-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid methyl ester (4), 2-phenyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid (5), 4'-methoxy-2',3',3'-tribromo-4',5',5'-trihydroxydiphenylacetic acid (6), and 3-bromo-5-hydroxy-4-methoxyphenylacetic acid (7) and its methyl ester (8), together with a known bromophenol, 3-bromo-5-hydroxy-4-methoxybenzoic acid (9), were isolated from the red alga Rhodomela confervoides. Their structures were elucidated by spectroscopic methods including IR, EIMS, FABMS, ESIMS, HRFABMS, HRESIMS, 1D and 2D NMR, and single-crystal X-ray structure analysis. Compounds 1-4, 8, and 9 were found inactive against several human cancer cell lines and microorganisms.     

Polyhalogenated monoterpenes from a tasmanian collection of the red seaweed Plocamium cartilagineum

Two new polyhalogenated monoterpenes (3E, 7E)-8-bromo-(2E)-chloromethylene-(5R, 6R)-dichloro-6-methyloctadien-1-al (1) and (1Z,3E,7E)-8,9-dibromo-(1Z,5R*, 6R*,9)-tetrachloro-6-methyloctatriene [corrected] (2), together with two known compounds (3 and 4), were isolated and identified from the red alga Plocamium cartilagineum collected along the eastern coast of Tasmania. The structures were established by spectroscopic techniques.     

Brominated sesquiterpenes from the red alga Laurencia obtusa

Four new sesquiterpenes, (8R)-8-bromo-10-epi-beta-snyderol (1), (8S)-8-bromo-beta-snyderol (2), 5-bromo-3-(3'-hydroxy-3'-methylpent-4'-enylidene)-2,4,4-trimethylcyclohexanone (3), and the epoxide 4, have been isolated from the chloroform-methanol extract of Laurencia obtusa, together with the three known compounds alpha-snyderol (5), alpha-snyderol acetate (6), and stigmasterol. The structures of the isolated compounds were elucidated through spectroscopic analyses. Compound 1 showed antimalarial activity, with IC(50) values of 2700 and 4000 ng/mL against the D6 and W2 clones of Plasmodium falciparum, respectively.     

Bromophenols from the red alga Rhodomela confervoides

Six new bromophenols, 3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)pyrocatechol (1), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-hydroxymethyldiphenylmethane (2), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-ethyloxymethyldiphenylmethane (3), (+/-)-2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propylaldehyde (4), (+/-)-2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propylaldehyde dimethyl acetal (5), and 3-bromo-4,5-dihydroxybenzoic acid methyl ester (6), together with eight known bromophenols, 3-bromo-4,5-dihydroxybenzaldehyde (7), 2,3-dibromo-4,5-dihydroxybenzyl alcohol (lanosol, 8), 2,3-dibromo-4,5-dihydroxybenzyl methyl ether (9), 2,3-dibromo-4,5-dihydroxybenzyl ethyl ether (10), 2,3-dibromo-4,5-dihydroxybenzylaldehyde (11), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (12), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethylpyrocatechol (13), and 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenyl methane (14), were isolated from the red alga Rhodomela confervoides. Their structures were elucidated by chemical and spectroscopic methods including IR, HRFABMS, and 1D and 2D NMR techniques.     

蝉翼藤抗氧化酮成分研究

目的：研究蝉翼藤抗氧化活性成分。方法：采用活性跟踪，利用各种色谱法分离，运用多种波谱技术(1D-NMR,2D-NMR和MS)鉴定结构。结果：从具有抗氧化活性的蝉翼藤根95%乙醇提取物的氯仿部位得到9个酮类化合物：1,2,5-三羟基-6,8-二甲氧基-酮(1), 1,5-二羟基-2,6,8-甲氧基-酮(2), 3,8-二羟基-1,4-二甲氧基-酮(3), 4,6-二羟基-1,5,7-三甲氧基-酮(4), 7-羟基-1,2,3,8-四甲氧基-酮(5), 1,7-二羟基-酮(6), 4-羟基-3,7-二甲氧基-酮(7), 1,7-二甲氧基-酮(8)和aucuparin(9)。结论：化合物1，2为新化合物,化合物3为新天然产物,化合物4，6为首次从该属中获得；化合物9在ABTS和FRAP模型中显示出显著的抗氧化活性；化合物1清除DPPH自由基能力的IC₅₀为0.31 mg·L^-1。ABTS和FRAP两个模型显示较高相关性(r=0.955 5)。     

Bioactive cardenolides from the stems and twigs of Nerium oleander

Four new cardenolide monoglycosides, cardenolides N-1 (1), N-2 (2), N-3 (3), and N-4 (4), were isolated from Nerium oleander, together with two known cardenolides, 5 and 12, and seven cardenolide monoglycosides, 6-11 and 13. The structures of compounds 1-4 were established on the basis of their spectroscopic data. The in vitro anti-inflammatory activity of compounds 1-13 was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). Compounds 1, 5, 6, and 11-13 were active at an IC50 value of less than 1 microM. The cytotoxicity of compounds 1-13 was evaluated against three human cell lines, normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), and human liver tumor cells (HepG2). Compounds 1, 4, 6, and 11-13 were active toward V-13 cells, and compounds 1, 11, and 12 were active toward HepG2 cells at IC50 values of less than 1 microM. Compounds 4, 5, 10, and 12 showed selective cell growth inhibitory activity toward V-13 tumor cells compared with that of parental normal WI-38 cells. The MDR-reversal activity of compounds 1-13 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compounds 4, 9, and 10 showed significant effects on calcein accumulation, compound 4 showing stronger activity than that of verapamil.     

Investigation of brominated tryptophan alkaloids from two thorectidae sponges: Thorectandra and Smenospongia

Chemical investigation of an NCI-DTP collection of Thorectandra sp. and a UCSC collection of Smenospongia sp. yielded six new brominated tryptophan derivatives: 6-bromo-1'-hydroxy-1',8-dihydroaplysinopsin (4), 6-bromo-1'-methoxy-1',8-dihydroaplysinopsin (5), 6-bromo-1'-ethoxy-1',8-dihydroaplysinopsin (6), (-)-5-bromo-N,N-dimethyltryptophan (7), (+)-5-bromohypaphorine (8), and 6-bromo-1H-indole-3-carboxylic acid methyl ester (11). Additionally, the known compounds aplysinopsin (1), 1',8-dihydroaplysinopsin (2), 6-bromo-1',8-dihydroaplysinopsin (3), (1H-indole-3-yl)acetic acid (9), and (6-bromo-1H-indol-3-yl)acetic acid methyl ester (10) were also encountered. The structures of 4-8 and 11 were confirmed on the basis of analysis of (1)H and (13)C (1D and 2D) NMR data as well as comparison to known compounds. Compounds 1, 3-8, 10, and 11 were found to inhibit the growth of Staphylococcus epidermidis with either weak or moderate MICs.     

Bromophenols coupled with methyl gamma-ureidobutyrate and bromophenol sulfates from the red alga Rhodomela confervoides

Four new bromophenols C-N coupled with methyl gamma-ureidobutyrate (1-4), a phenylethanol bromophenol (5), and three phenylethanol sulfate bromophenols (6-8) have been isolated from polar fractions of an ethanolic extract of the red alga Rhodomela confervoides. On the basis of spectroscopic evidence including HRMS and 2D NMR data, the structures of the new compounds were determined as methyl N'-(2,3-dibromo-4,5-dihydroxybenzyl)-gamma-ureidobutyrate (1), methyl N,N'-bis(2,3-dibromo-4,5-dihydroxybenzyl)-gamma-ureidobutyrate (2), methyl N'-[3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyl]-gamma-ureidobutyrate (3), methyl N'-(2,3-dibromo-4,5-dihydroxybenzyl)-N'-[3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyl]-gamma-ureidobutyrate (4), 2,3-dibromo-4,5-dihydroxyphenylethanol (5), 2,3-dibromo-4,5-dihydroxyphenylethanol sulfate (6), 3-bromo-4,5-dihydroxyphenylethanol sulfate (7), and 3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxyphenylethanol sulfate (8). The cytotoxicity of all compounds was evaluated against several human cancer cell lines including human colon cancer (HCT-8), hepatoma (Bel7402), stomach cancer (BGC-823), lung adenocarcinoma (A549), and human ovarian cancer (A2780). Among them, the phenylethanol and the phenylethanol sulfate bromophenols (5-8) showed moderate cytotoxicity against all tested cell lines.     

New bromotyrosine derivatives from an association of two sponges, Jaspis wondoensis and Poecillastra wondoensis

Three new bromotyrosine derivatives (4-6) were isolated from an association of two sponges, Jaspis wondoensis and Poecillastra wondoensis, along with the previously described (E,E)-psammaplin A (1), (E,Z)-psammaplin A (2), psammaplin D (3), bisaprasin (7), and (3-bromo-4-hydroxyphenyl)acetonitrile (8). The structures of the new compounds were established on the basis of NMR and MS spectroscopic analysis. The compounds 1, 3, and 5-7 displayed significant cytotoxicity against human lung (A549), ovarian (SK-OV-3), skin (SK-MEL-2), CNS (XF498), and colon (HCT15) cancer cell lines. Compounds 3-7 were further evaluated for antibacterial activity against methicillin- or ofloxacin-resistant Staphylococcus strains. Compound 4 exhibited more potent antibacterial activity than meropenem against several strains.     

Brominated labdane-type diterpenoids from an Okinawan Laurencia sp

From an unidentified species of Laurencia collected from Okinawan waters two novel brominated metabolites, 1 and 2, along with known halogenated compounds, 2,10-dibromo-3-chloro-alpha-chamigrene (3) and microcladallene A (4), were isolated and identified. The structures of these new compounds were established as ent-labdane-type bromoditerpenes, (1S,3R,5S,6S,8S,9S,10R,13R)-1-acetoxy-3-bromo-6-hydroxy-8,13-epoxy-labd-14-ene (1) and (3R,5S,6S,8S,9S,10R,13R)-3-bromo-6-hydroxy-8,13-epoxylabd-14-en-1-one (2), by interpretation of their spectroscopic data as well as by X-ray crystallographic analysis.     

Biological activity of Anthraquinones and Triterpenoids from Prismatomeris fragrans

A new 1,3-dihydroxy-2-methyl-5,6-dimethoxyanthraquinone (1); six known anthraquinones, nordamnacanthal (2), damnacanthal (3), rubiadin (4), rubiadin-1-methyl ether (5), lucidin-ω-methyl ether (6), and 1-hydroxy-2-hydroxymethyl-3-methoxyanthraquinone (7); a β-sitosterol (8); together with two known triterpenoids, β-acetylolean-12-en-28-olic acid (9), and 3β-O-acetyl-11,12-epoxyolean-28,13-olide (10) were isolated from the roots and stems of Prismatomeris fragrans. Their structures were established on the basis of spectral data. This is the first isolation of compounds 2, 6, 7, 9 and 10 from Prismatomeris genus. The isolated compounds were evaluated in antiplasmodial, antituberculosis, antifungal and anticancer cell lines tests. The bioactivity assays showed that only 9 exhibited moderate antimalarial activity, 2 and 3 exhibited antifungal activity while 2, 3, 4, 7 and 9 showed antituberculosis activity. In addition, compounds 2, 3 and 7 exhibited cytotoxicity to BC cell line while 1, 1a (the methyl ether derivative of 1), 2, 3, 4, 5, and 9 exhibited cytotoxicity to NCI-H187 cell line.     

Alkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A receptors in Vitro

A 70% ethanol extract of California poppy (Eschscholzia californica) was able to bind to 5-HT(1A) and 5-HT(7) receptors at 100 mug/mL. The subsequent isolation procedure yielded the known alkaloids californidine (1), escholtzine (2), N-methyllaurotetanine (3), caryachine (4), and O-methylcaryachine (5), along with a new pavine alkaloid, 6S,12S-neocaryachine-7-O-methyl ether N-metho salt (7). The structure of 7 was determined by spectroscopic data interpretation, while the absolute stereochemistry was determined by means of circular dichroism. From the results obtained from the radioligand-binding assay of the pure compounds, including the commercially available protopine (6), it was evident that the activity on the 5-HT(1A) receptor was at least partly due to the presence of the aporphine alkaloid 3, which showed the highest inhibition of [(3)H]8-hydroxy-2-(di-N-propylamino)tetralin ([(3)H]8-OH-DPAT) binding with an EC(50) value of 155 nM and a K(i) of 85 nM.     

Cytotoxic flavonoids from Platymiscium floribundum

Two new isoflavonoids, 7-hydroxy-6,4'-dimethoxy-isoflavonequinone (1) and 2'-hydroxy-6,4',6' ',4' '-tetramethoxy-[7-O-7' ']-bisisoflavone (2), and seven other known flavonoids, 3-hydroxy-9-methoxypterocarpan (medicarpin), 3,10-dihydroxy-9-methoxypterocarpan, 3,9-dimethoxypterocarpan (homopterocarpin) (3), 2,3,9-trimethoxypterocarpan (4), 3,4-dihydroxy-9-methoxypterocarpan (vesticarpan) (5), 2',4,4'-trihydroxychalcone (isoliquiritigenin), and 7,4'-dihydroxyflavanone (liquiritigenin) (6), were isolated from the heartwood of Platymiscium floribundum. The structures of compounds 1 and 2 were established by spectroscopic methods. Compounds 3-6 showed cytotoxic activity when evaluated against five human cancer cell lines in vitro.     

Bromophenols from the marine red alga Polysiphonia urceolata with DPPH radical scavenging activity

Three new (1-3) and three known (4-6) bromophenols were isolated and identified from the marine red alga Polysiphonia urceolata. On the basis of extensive analysis of spectroscopic data, the structures of these compounds were determined to be 7-bromo-9,10-dihydrophenanthrene-2,3,5,6-tetraol (1), 4,7-dibromo-9,10-dihydrophenanthrene-2,3,5,6-tetraol (2), 1,8-dibromo-5,7-dihydrodibenzo[ c,e]oxepine-2,3,9,10-tetraol (3), urceolatol (4), 3-bromo-4,5-dihydroxybenzaldehyde (5), and 3,5-dibromo-4-hydroxybenzaldehyde (6). Each of the isolated compounds was evaluated for alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical scavenging activity, and all were found to be potent, with IC50 values ranging from 6.1 to 35.8 microM, compared to the positive control, butylated hydroxytoluene (BHT), with an IC50 of 83.8 microM.     

Antioxidant and free-radical scavenging activity of constituents of the leaves of Tachigalia paniculata

Two new myricetin glycosides, myricetin 7-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (1) and myricetin 7-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (2), together with the known compounds quercetin 3-O-beta-D-glucopyranoside (3), quercetin 3-O-alpha-L-rhamnopyranoside (4), quercetin 3-O-beta-D-galactopyranoside (5), methyl gallate (6), isovanillin (7), 4-hydroxymethylbenzoate (8), 3,4-dihydroxymethylbenzoate (9), and caffeoyl aldehyde (10) were isolated from the leaves of Tachigalia paniculata. The structures of these compounds were determined by spectroscopic methods. Their antioxidant activity was determined by measuring free-radical scavenging effects using three different assays, namely, the Trolox Equivalent Antioxidant Capacity (TEAC) assay, the coupled oxidation of beta-carotene and linoleic acid (autoxidation assay), and the inhibition of xanthine oxidase activity. Compounds 1, 2, and 6 showed activity in the TEAC test, compounds 5-7 and 10 were moderately active in the autoxidation assay, while compounds 1 and 2 were the most potent of the isolates in the xanthine oxidase test.     

Laurendecumallenes A-B and laurendecumenynes A-B, halogenated nonterpenoid C(15)-acetogenins from the marine red alga Laurencia decumbens

Four new halogenated nonterpenoid C(15)-acetogenins, 4:7,6:13-bisepoxy-9,10-diol-1,12-dibromopentadeca-1,2-diene (1, laurendecumallene A), 4:7,6:12-bisepoxy-9,10-diol-1,13-dibromopentadeca-1,2-diene (2, laurendecumallene B), (3Z)-6:10,7:13-bisepoxy-12-bromo-9-hydroperoxylpentadeca-3-en-1-yne (3, laurendecumenyne A), and (3Z)-6:10,9:13-bisepoxy-12-bromo-7-chloropentadeca-3-en-1-yne (4, laurendecumenyne B), together with one known halogenated C(15)-acetogenin elatenyne (5) were isolated and identified from the organic extract of the marine red alga Laurencia decumbens. Their structures and relative stereochemistry were established by means of spectroscopic analysis including UV, IR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and 1D and 2D NMR techniques. All these metabolites were submitted for the cytotoxic assay against tumor cell line A549 (human lung adenocarcinoma), but all of them were found inactive (IC(50) > 10 microg/mL).     

Benzophenones and biflavonoids from Rheedia edulis

Two new polyisoprenylated benzophenones, 32-hydroxy-ent-guttiferone M (1) and 6-epi-guttiferone J (2), along with seven known compounds, 6-epi-clusianone (3), guttiferone A (4), xanthochymol (5), guttiferone E (6), isoxanthochymol (7), (+)-volkensiflavone (8), and (+)-morelloflavone (9), were identified from the seeds and rinds of Rheedia edulis. Compounds 1-3 and 5-9 have been isolated and identified from this species for the first time. The structures of the new compounds were elucidated mainly by analysis of their 1D and 2D NMR spectroscopic data, and their absolute configurations were determined by comparison of their experimental optical rotation and electronic circular dichroism measurements with those values predicted by DFT calculations. Compound 1 showed significant antioxidant activity in both DPPH and ABTS free radical scavenging assays, whereas compound 2 was inactive.     

Gliotoxin analogues from a marine-derived fungus, Penicillium sp., and their cytotoxic and histone methyltransferase inhibitory activities

Seven gliotoxin-related compounds were isolated from the fungus Penicillium sp. strain JMF034, obtained from deep sea sediments of Suruga Bay, Japan. These included two new metabolites, bis(dethio)-10a-methylthio-3a-deoxy-3,3a-didehydrogliotoxin (1) and 6-deoxy-5a,6-didehydrogliotoxin (2), and five known metabolites (3-7). The structures of the new compounds were elucidated by analysis of spectroscopic data and the application of the modified Mosher's analysis. All of the compounds exhibited cytotoxic activity, whereas compounds containing a disulfide bond showed potent inhibitory activity against histone methyltransferase (HMT) G9a. None of them inhibited HMT SET7/9.