Multi-target-directed triazole derivatives as promising agents for the treatment of Alzheimer’s disease

A novel series of triazole-based compounds have been designed, synthesised and evaluated as multi-target-directed ligands (MTDLs) against Alzheimer disease (AD). The triazole-based compounds have been designed to target four major AD hallmarks that include Aβ aggregation, metal-induced Aβ aggregation, metal dys-homeostasis and oxidative stress. Among the synthesised compounds, 6n having o-CF₃ group on the phenyl ring displayed most potent inhibitory activity (96.89% inhibition, IC₅₀ = 8.065 ± 0.129 μM) against Aβ₄₂ aggregation, compared to the reference compound curcumin (95.14% inhibition, IC₅₀ = 6.385 ± 0.009 μM). Compound 6n disassembled preformed Aβ₄₂ aggregates as effectively as curcumin. Furthermore, 6n displayed metal chelating ability and significantly inhibited Cu²⁺-induced Aβ₄₂ aggregation and disassembled preformed Cu²⁺-induced Aβ₄₂ aggregates. 6n successfully controlled the generation of the reactive oxygen species (ROS) by preventing the copper redox cycle. In addition, 6n did not display cytotoxicity and was able to inhibit toxicity induced by Aβ₄₂ aggregates in SH-SY5Y cells. The preferred binding regions and key interactions of 6n with Aβ₄₂ monomer and Aβ₄₂ protofibril structure was evaluated with molecular docking. Compound 6n binds preferably to the C-terminal region of Aβ₄₂ that play a critical role in Aβ₄₂ aggregation. The results of the present study highlight a novel triazole-based compound, 6n, as a promising MTDL against AD.     

Anti-inflammatory activity of flavonoids from Chrozophora tinctoria

Chemical investigation of Chrozophora tinctoria (L.) A. Juss. growing in Saudi Arabia revealed the isolation of two new acylated flavonoids identified as acacetin-7-O-β-d-[α-l-rhamnosyl(1 → 6)]3″-E-p-coumaroyl glucopyranoside (4) and apigenin-7-O-(6″-Z-p-coumaroyl)-β-d-glucopyranoside (5), in addition to amentoflavone (1), apigenin-7-O-β-d-glucopyranoside (2), apigenin-7-O-6″-E-p-coumaroyl-β-d-glucopyranoside (3) and rutin (6). The structures of isolated compounds were established by 1D, 2D NMR and HRESIMS spectral data, in addition to comparison with literature data. The anti-inflammatory activities of isolated compounds were assessed by measuring the levels of IL-1β, IL-6, TNF-α and PGE₂ in the supernatant media of human peripheral blood mononuclear cells (PBMCs) stimulated by phytohaemagglutinin (PHA). At a concentration of 100 μM, compounds 1, 2, 4 and 6 significantly decreased Il-1β, Il-6 and PGE₂ to nearly normal values. All tested compounds caused a dose-dependent decrease in TNF-α level but failed to reach that of the control values.     

Anti-influenza patchoulol-type sesquiterpenoids from Pogostemon cablin

Four new patchoulol-type sesquiterpenoids, including 6α,9β-dihydroxypatchoulol 6-O-β-d-glucopyranoside (1), 6α-hydroxypatchoulol 6-O-β-d-glucopyranoside (2), 3α,9β-dihydroxypathoulol (3), and 4β-hydroxynorpatchoulol 4-O-β-d-glucopyranoside (10), were isolated from the roots of Pogostemon cablin (Blanco) Benth, together with eleven known sesquiterpenoids. Their structures were elucidated on the basis of extensive NMR spectral and high resolution mass spectrometry analysis. This is the second report of patchoulol glucopyranoside from P. cablin and compound 10 represented as the first example of nor-patchoulol glucopyranoside. The anti-influenza virus activities of 1–10 against A/WSN/33/2009 and A/Puerto Rico/8/1934 strains (tamiflu resistant viruses) were evaluated. Compounds 2β,12-dihydroxypathoulol (5) and (5R)-5-hydroxypatchoulol (8) exhibited moderate anti-influenza activity against A/WSN/33/2009 strain with EC₅₀ value of 52.7 μM and 49.6 μM (positive control oseltamivir, EC₅₀ = 6.75 μM). Compounds 8 and pogostol (12) showed potent anti-influenza activity against A/Puerto Rico/8/1934 strain with EC₅₀ values of 3.06 μM and 0.07 μM, respectively, versus the postive control (amantadine, EC₅₀ = 67.9 μM).     

Antiplasmodial sesquiterpenes from the seeds of Salacia longipes var. camerunensis

Phytochemical investigation of the seeds of Salacia longipes var. camerunensis led to the isolation of four sesquiterpenoid derivatives, salaterpene A (1) (1α,2β,8β-triacetoxy-6β,9β-dibenzoyloxy-4β-hydroxy-dihydro-β-agarofuran), salaterpene B (2) (1α,2β,8β-triacetoxy-9β-benzoyloxy-6β-cinnamoyloxy-4β-hydroxy-dihydro-β-agarofuran), salaterpene C (3) (1α,2β-diacetoxy-6β,9β-dibenzoyloxy-4β-hydroxy-dihydro-β-agarofuran) and salaterpene D (4) (2β-acetoxy-1α,6β-dibenzoyloxy-4β-hydroxy-9β-nicotinoyloxy-dihydro-β-agarofuran) together with two known compounds (5 and 6). The structures of the compounds were established by means of NMR spectroscopy. Compounds 1–4 and 6 were tested in vitro for their antiplasmodial activity against Plasmodium falciparum chloroquine-resistant strain W2. All the tested compounds exhibited a moderate potency with IC₅₀ below 2.7 μM.     

6-Methoxyflavonols from the aerial parts of Tetragonia tetragonoides (Pall.) Kuntze and their anti-inflammatory activity

Dried aerial parts of Tetragonia tetragonoides were extracted with 70% EtOH, and the evaporated residue was successively separated into EtOAc, n-BuOH, and H₂O fractions. As a result of repeated SiO₂, ODS, and Sephadex LH-20 column chromatography, four new 6-methoxyflavonol glycosides (2–4, 8) along with four known ones (1, 5–7) were isolated. Several spectroscopic data led to determination of chemical structures for four new 6-methoxyflavonol glycosides (2–4, 8) and four known ones, 6-methoxykaempferol 3-O-β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyl-7-O-(6‴′-(E)-caffeoyl)-β-d-glucopyranoside (1), 6-methoxyquercetin (5), 6-methoxykaempferol (6), and 6-methoxykaempferol 7-O-β-d-glucopyranoside (7). Methoxyflavonol glycosides 2–8 also have never been reported from T. tetragonoides in this study. 6-Methoxyflavonols 5 and 6 showed high radical scavenging potential in DPPH and ABTS test. Also, all compounds showed significant anti-inflammatory activities such as reduction of NO and PGE₂ formation and suppression of TNF-α, IL-6, IL-1β, iNOS, and COX-2 expression in LPS-stimulated RAW 264.7 macrophages. In general, the aglycones exhibited higher activity than the glycosides. In addition, quantitative analysis of 6-methoxyflavonols in the T. tetragonoides aerial parts extract was conducted through HPLC.     

Specific spectral assignments for acetoxyl-group resonances in proton magnetic resonance spectra of methyl β-D-glucopyranoside tetraacetate and related derivatives

Methyl β-D-glucopyranoside tetraacetates (1) having a trideuterioacetyl group at O-2 (1a), O-3, (1b), O-4 (1c), and O-6 (1d) were synthesized by unambiguous routes to permit assignment of each individual acetoxyl-group signal in the p.m.r. spectrum of 1. The 6-acetoxyl resonance appears at lower field than signals of the other acetoxyl groups in carbon tetrachloride, chloroform-d, and methyl sulfoxide-d₆, but in pyridine-d₅ and benzene-d₆, the 2-acetoxyl-group signal appears at lower field. The acetoxyl resonances of methyl 2,3,4-tri-O-acetyl-6-O-trityl-β-D-glucopyranoside (2), methyl 2,3,4-tri-O-acetyl-β-D-glucopyranoside (3), methyl 2,3-di-O-acetyl-4,6-O-benzylidene-β-D-glucopyranoside (5), methyl 2,3-di-O-acetyl-β-D-glucopyranoside (6), methyl 2,3,6-tri-O-acetyl-β-D-glucopyranoside (7), and methyl 2,3-di-O-acetyl-6-O-trityl-β-D-glucopyranoside (12) were assigned similarly after synthesis of the 2-(trideuterioacetyl) (2a, 3a, 5a, 6a, 7a, and 12a), 3-(trideuterioacetyl) (2b, 3b, 5b, 6b, 7b, and 12b), 4-(trideuterioacetyl) (2c and 3c), and 6-(trideuterioacetyl) (7c) analogues. In chloroform-d and benzene-d₆, the 4-acetoxyl resonance appeared at about 0.3 p.p.m. to higher field than the other acetoxyl-group signals of 2. In chloroform-d and methyl sulfoxide-d₆, the 3-acetoxyl resonance is observed at highest field in compounds 1, 3, and 5. In all of these instances, the 4-hydroxyl group is substituted by an acetyl or benzylidene group. When no 4-substituent is present (compounds 6, 7, and 12), the 3-acetoxyl group resonates at lower field than the other acetoxyl groups.     

Eudesmane-type sesquiterpenes from the liverwort Apomarsupella revolute

Phytochemical investigation of the Et₂O extract of liverwort Apomarsupella revolute led to isolation and identification of five new eudesmane-type sesquiterpenoids, 6β-hydroxy-9β-acetoxy-eudesma-4,11-dien (1), 6β-hydroxy-9β-acetoxy-eudesma-4,11-dien-3-one (2), 5α,6β-dihydroxy-9β-acetoxy-eudesma-4(15),11-dien (3) 4β-hydroxy-9β-acetoxy-11,12,13-trinor-5-eudesmen-7-one (4) and 4β-methox-9β-acetoxy-11,12,13-trinor-5-eudesmen-7-one (5), two of which were trinorsesquiterpenoids. Their structures were established unequivocally on the basis of spectroscopic data analysis. All compounds were preliminary bioscreened for their cytotoxicities and antifungal activities.     

Synthesis of the (1→6)-linked thiodisaccharide of galactofuranose: Inhibitory activity against a β-galactofuranosidase

A new (1→6)-linked thiodisaccharide formed by two galactofuranosyl units has been synthesized. Methyl (methyl α,β-d-galactofuranosid)uronate was employed as the starting compound, which was per-O-silylated with TBSCl and reduced with LiAlH₄ to afford methyl 2,3,5-tri-O-tert-butyldimethylsilyl-β-d-galactofuranoside (2β) as a key precursor for the preparation of methyl per-O-tert-butyldimethylsilyl-6-thio-β-d-galactofuranoside (12). The free thiol group of 12 was glycosylated and the product O-deprotected to afford the target β-d-Galf-S-(1→6)-β-d-Galf-OMe (14). The conformations of this thiodisaccharide were preliminarily studied using combined theoretical calculations and NMR data. Furthermore, the glycomimetic 14 showed to be a competitive inhibitor of the β-galactofuranosidase from Penicillum fellutanum (K_i = 3.62 mM).     

New derivatives of ursolic acid through the biotransformation by Bacillus megaterium CGMCC 1.1741 as inhibitors on nitric oxide production

Microbial transformation of ursolic acid (1) by Bacillus megaterium CGMCC 1.1741 was investigated and yielded five metabolites identified as 3-oxo-urs-12-en-28-oic acid (2); 1β,11α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3); 1β-hydroxy-3-oxo-urs-12-en-28, 13-lactoe (4); 1β,3β, 11α-trihydroxyurs-12-en-28-oic acid (5) and 1β,11α-dihydroxy-3-oxo-urs-12-en-28-O-β-d-glucopyranoside (6). Metabolites 3, 4, 5 and 6 were new natural products. Their nitric oxide (NO) production inhibitory activity was assessed in lipopolysaccharide (LPS) – stimulated RAW 264.7 cells. Compounds 3 and 4 exhibited significant activities with the IC₅₀ values of 1.243 and 1.711 μM, respectively. A primary structure-activity relationship was also discussed.     

A new phenylpropanoid and an alkylglycoside from Piper retrofractum leaves with their antioxidant and α-glucosidase inhibitory activity

Two new compounds, piperoside (1) and isoheptanol 2(S)-O-β-d-xylopyranosyl (1→6)-O-β-d-glucopyranoside (11), along with 10 known compounds 3,4-dihydroxyallylbenzene (2), 1,2-di-O-β-d-glucopyranosyl-4-allylbenzene (3), tachioside (4), benzyl-O-β-d-glucopyranoside (5), icariside F₂ (6), dihydrovomifoliol-3′-O-β-d-glucopyranoside (7), isopropyl O-β-d-glucopyranoside (8), isopropyl primeveroside (9), n-butyl O-β-d-glucopyranoside (10), isoheptanol 2(S)-O-β-d-apiofuranosyl-(1→6)-O-β-d-glucopyranoside (12), were isolated from the leaves of Piper retrofractum. Their structures were determined from 1D-NMR, 2D-NMR, and HR-ESI-MS spectral, a modified Mosher’s method, and comparisons with previous reports. All of the isolated compounds showed modest α-glucosidase inhibitory (4.60 ± 1.74% to 11.97 ± 3.30%) and antioxidant activities under the tested conditions.     

New triterpene saponins from Phryna ortegioides

Four new and three known oleanane-type saponins have been isolated from the methanolic extract of Phryna ortegioides, a monotypic and endemic taxon of Caryophyllaceae.The structures of the new compounds were determined as gypsogenic acid 28-O-β-d-glucopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→6)-O-β-d-glucopyranosyl ester (1), 3-O-α-l-arabinofuranosyl-gypsogenic acid 28-O-β-d-glucopyranosyl-(1→3)-O-[β-d-glucopyranosyl-(1→6)]-O-β-d-glucopyranosyl ester (2), 3-O-α-l-arabinofuranosyl-gypsogenic acid 28-O-β-d-glucopyranosyl-(1→3)-O-[β-d-glucopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→6)-O-]-β-d-glucopyranosyl ester (3), 3-O-α-l-arabinofuranosyl-16α-hydroxyolean-12-en-23,28-dioic acid-28-O-β-d-glucopyranosyl-(1→3)-O-[β-d-glucopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→6)]-O-β-d-glucopyranosyl ester (4). Their structures were established by a combination of one- and two-dimensional NMR techniques, and mass spectrometry. Noteworthy, none of isolated compounds possesses as aglycone moiety gypsogenin, considered a marker of Caryophyllaceae family.The cytotoxic activity of the isolated compounds was evaluated against three cancer cell lines including A549 (human lung adenocarcinoma), A375 (human melanoma) and DeFew (human B lymphoma) cells. Only compound 6 showed a weak activity against A375 and DeFew cell lines with IC₅₀ values of 77 and 52 μM, respectively. None of the other tested compounds, in a range of concentrations between 12.5 and 100 μM, caused a significant reduction of the cell number.     

Ring-opening reactions of sucrose epoxides: Synthesis of 4′-derivatives of sucrose

The 2,1′-O-isopropylidene derivative (1) of 3-O-acetyl-4,6-O-isopropylidene-α-d-glucopyranosyl 6-O-acetyl-3,4-anhydro-β-d-lyxo-hexulofuranoside and 2,3,4-tri-O-acetyl-6-O-trityl-α-d-glucopyranosyl 3,4-anhydro-1,6-di-O-trityl-β-d-lyxo-hexulofuranoside have been synthesised and 1 has been converted into 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,6-di-O-acetyl-3,4-anhydro-β-d-lyxo-hexulofuranoside (2). The S_N2 reactions of 2 with azide and chloride nucleophiles gave the corresponding 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-azido-4-deoxy-β-d-fructofuranoside (6) and 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-chloro-4-deoxy-β-d-fructofuranoside (8), respectively. The azide 6 was catalytically hydrogenated and the resulting amine was isolated as 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 4-acetamido-1,3,6-tri-O-acetyl-4-deoxy-β-d-fructofuranoside. Treatment of 5 with hydrogen bromide in glacial acetic acid followed by conventional acetylation gave 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-bromo-4-deoxy-β-d-fructofuranoside. Similar S_N2 reactions with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,6-di-O-acetyl-3,4-anhydro-β-d-ribo-hexulofuranoside (12) resulted in a number of 4′-derivatives of α-d-glucopyranosyl β-d-sorbofuranoside. The regiospecific nucleophilic substitution at position 4′ in 2 and 12 has been explained on the basis of steric and polar factors.     

Anti-HIV protease triterpenoids from the acid hydrolysate of Panax ginseng

Three artificial triterpenoids, (20R)-20,25-epoxy-dammaran-2-en-6α,12β-diol (1), (20R)-20,25-epoxy-3-methyl-28-nordammaran-2-en-6α,12β-diol (2) and isodehydroprotopanaxatriol (3), were isolated from an acidic hydrolysate of Panax ginseng C.A. Meyer, along with three known triterpenes, (20R)-panaxadiol (4), (20R)-panaxatriol (5) and oleanolic acid (6). Compounds 1–3 and 6 showed inhibitory activity against HIV-1 protease with IC₅₀ of 10.5, 10.3, 12.3 and 6.3 μM, respectively. The results indicated that acid treatment of Ginseng extract could produce diverse structures with interesting bioactivity.     

Two new cembranic diterpenoids from the flowers of Nicotiana tabacum L.

Two new cembranoids, together with fifteen known ones, were isolated from the flowers of Nicotiana tabacum L. The structures of the new compounds were established as (1βH,2E,4αOH,6αOH,7E,10αH,11αH,12βOH)-10,11-epoxy-2,7-cembradiene-4,6,12-triol (1) and (1βH,2E,4αOH,6αOH,7E,10βH,11βH,12αOH)-10,11-epoxy-2,7-cembradiene-4,6, 12-triol (2) by using spectroscopic analysis, including HRESIMS, IR, one- and two-dimensional NMR. A plausible biogenetic relationship of the isolated cembranoids was proposed. The antitumor activities of selected compounds against a panel of three human cancer HepG2, A549 and HCT-116 cell lines were evaluated by the MTT assay. Compound 5 exhibited moderate activity against Hep-G2 cell lines with an IC₅₀ value of 14.38 μM.     

Seven new triterpenoids from the aerial parts of Ilex cornuta and protective effects against H2O2-induced myocardial cell injury

Seven new triterpenoids (1–7), together with two known ones (8–9), were isolated from the aerial parts ofIlex cornuta. The leaves of I. cornuta are the major source of “Kudingcha”, a popular herbal tea consumed in China and other countries. The structures of compounds 1–7 were determined as 20-epi-urs-12,18-dien-28-oic acid 3β-O-α-l-arabinopyranoside (1), 20-epi-urs-12,18-dien-28-oic acid 2′-O-acetyl-3β-O-α-l-arabinopyranoside (2), 20-epi-urs-12,18-dien-28-oic acid 3β-O-β-d-glucuronopyranoside-6-O-methyl ester (3), 3β,23-dihydroxy-20-epi-urs-12,18-dien-28-oic acid (4), 23-hydroxy-20-epi-urs-12,18-dien-28-oic acid 3β-O-α-l-arabinopyranoside (5), 23-hydroxy-20-epi-urs-12,18-dien-28-oic acid 3β-O-β-d-glucuronic acid (6), 23-hydroxy-20-epi-urs-12,18-dien-28-oic acid 3β-O-β-d-glucuronopyranoside-6-O-methyl ester (7), on the basis of spectroscopic analyses (IR, ESI–MS, HR-ESI–MS, 1D and 2D NMR) and chemical reactions. Protective effects against H₂O₂-induced H9c2 cardiomyocyte injury were tested in vitro for compounds 1–9, and the data showed that compound 4 had significant cell-protective effect. Compounds 1-9 did not show significant DPPH radical scavenging activity.     

Enzymatic synthesis of poly-N-acetyllactosamines as potential substrates for endo-β-galactosidase-catalyzed hydrolytic and transglycosylation reactions

Enzymatic synthesis of GlcNAc-terminated poly-N-acetyllactosamine β-glycosides GlcNAcβ1,3(Galβ1,4GlcNAcβ1,3)_nGalβ1,4GlcNAcβ-pNP (n=1–4) was demonstrated using a transglycosylation reaction of Escherichia freundii endo-β-galactosidase. The enzyme catalyzed a transglycosylation reaction on GlcNAcβ1,3Galβ1,4GlcNAcβ-pNP (1), which served both as a donor and an acceptor, and converted 1 into p-nitrophenyl β-glycosides GlcNAcβ1,3(Galβ1,4GlcNAcβ1,3)₁Galβ1,4GlcNAcβ-pNP (2), GlcNAcβ1,3(Galβ1,4GlcNAcβ1,3)₂Galβ1,4GlcNAcβ-pNP (3), GlcNAcβ1,3(Galβ1,4GlcNAcβ1,3)₃Galβ1,4GlcNAcβ-pNP (4) and GlcNAcβ1,3(Galβ1,4GlcNAcβ1,3)₄Galβ1,4GlcNAcβ-pNP (5). When 2 was used as an initial substrate, it led to the preferential synthesis of nonasaccharide β-glycoside 4 to heptasaccharide β-glycoside 3. This suggests that 4 is directly synthesized by transferring the tetrasaccharide unit GlcNAcβ1,3Galβ1,4GlcNAcβ1,3Gal to nonreducing end GlcNAc residue of 2 itself. The efficiency of production of poly-N-acetyllactosamines by E. freundii endo-β-galactosidase was significantly enhanced by the addition of BSA and by a low-temperature condition. Resulting 2 and 3 were shown to be useful for studying endo-β-galactosidase-catalyzed hydrolytic and transglycosylation reactions.     

Polyhydroxylated steroids from an endophytic fungus, Chaetomium globosum ZY-22 isolated from Ginkgo biloba

A novel polyhydroxylated C₂₉-sterol, 25ξ-methyl-22-homo-5α-cholest-7,22-diene-3β,6β,9α-triol, designated globosterol (1), together with one known tetrahydroxylated ergosterol (22E, 24R)-ergosta-7,22-diene-3β,5α,6β,9α-tetraol (2) has been isolated from the cultures of an endophytic fungus, Chaetomium globosum ZY-22 originated from the plant Ginkgo biloba. The structures and relative configurations of 1 and 2 were established on the basis of extensive spectroscopic analyses including 1D and 2D NMR (¹H-¹H COSY, HSQC, HMBC, and NOESY) experiments and comparison with the literature. Globosterol (1) possesses an unprecedented 25-methyl Δ²²-C₁₀-side chain and Δ⁷-3β,6β,9α-hydroxy-steroid nucleus, which represents the first example for C₂₉-steroids of the group.     

A new ursane and a new oleanane triterpene acids from the whole plant of Spermacoce latifolia

A phytochemical study on the whole plant of Spermacoce latifolia led to the isolation of a new ursane triterpene acid, 3β,6β,23-trihydroxy-urs-12,20(30)-dien-28-oic acid (1), and a new oleanane triterpene acid, 3β,6β,29-trihydroxy-olean-12-en-28-oic acid (2), together with seven known triterpenic acids (3–9). Their structures were established on the basis of detailed spectroscopic analysis, including one- and two-dimensional NMR, ESI–MS and HR–ESI–MS techniques. All the compounds were isolated from S. latifolia for the first time. Compounds 3, 5, 6 and 9 were found to show in vitro growth inhibitory activity against three assayed human cancer cell lines MCF-7, NCI-H460 and HepG-2 with IC₅₀ values from 9.53 to 80.20 mM. Compounds 1 and 3–9 were further revealed to show significantly in vitro α-glucosidase inhibitory activity with IC₅₀ values from 0.009 to 0.422 mM, most of which were more potent than the reference compound acarbose (IC₅₀ 0.409 mM).     

5-Hydroxyindole-type alkaloids,as Candida albicans isocitrate lyase inhibitors,from the tropical sponge Hyrtios sp.

Chemical investigations of the tropical marine sponge Hyrtios sp. have resulted in the isolation of a new alkaloid, 1-carboxy-6-hydroxy-3,4-dihydro-β-carboline (1) together with the known metabolites, 6-hydroxy-3,4-dihydro-1-oxo-β-carboline (2), 5-hydroxy-1H-indole-3-carboxylic acid methyl ester (3), serotonin (4), hyrtiosin A (5), 5-hydroxyindole-3-carbaldehyde (6), and hyrtiosin B (7). Their structures were elucidated on the basis of mass spectrometry and detailed 2D NMR spectroscopic data. Hyrtiosin B (7) displayed a potent inhibitory activity against isocitrate lyase (ICL) of Candida albicans with an IC₅₀ value of 89.0 μM.     

A flavone C-Glycoside from Styela plicata

A known flavonoid triglycoside, apigenin 6-C-[α-_L-arabinopyranosyl-(1‴→2″)-β-_D-glucopyranoside]-7-O-β-_D- glucopyranoside (1), was isolated from the n-butanol extract of Styela plicata for the first time. The structure of 1 was established by spectroscopic methods and direct comparison with authentic samples on HPLC after acid hydrolysis as a new marine natural flavonoid. This work contributes to expand the knowledge about the chemical compositions of S. plicata and the chemotaxonomy of ascidians.