Montamine, a unique dimeric indole alkaloid, from the seeds of Centaurea montana (Asteraceae), and its in vitro cytotoxic activity against the CaCo2 colon cancer cells

Reversed-phase HPLC analysis of the methanol extract of the seeds of Centaurea montana afforded a flavanone, montanoside (4), six epoxylignans, berchemol (7), berchemol 4′-O-β-d-glucoside (5), pinoresinol (10), pinoresinol 4-O-β-d-glucoside (8), pinoresinol 4,4′-di-O-β-d-glucoside (6), pinoresinol 4-O-apiose-(1→2)-β-d-glucoside (9), two quinic acid derivatives, trans-3-O-p-coumaroylquinic acid (1), cis-3-O-p-coumaroylquinic acid (2), and eight indole alkaloids, tryptamine (3), N-(4-hydroxycinnamoyl)-5-hydroxytryptamine (11), cis-N-(4-hydroxycinnamoyl)-5-hydroxytryptamine (12), centcyamine (16), cis-centcyamine (17), moschamine (13), cis-moschamine (14) and a dimeric indole alkaloid, montamine (15). While the structures of two new compounds, montanoside (4) and montamine (15), were established unequivocally by UV, IR, MS and a series of 1D and 2D NMR analyses, all known compounds were identified by comparison of their spectroscopic data with literature data. The antioxidant properties of these compounds were assessed by the DPPH assay, and their toxicity towards brine shrimps and cytotoxicity against CaCo-2 colon cancer cells were evaluated by the brine shrimp lethality and the MTT cytotoxicity assays, respectively. The novel dimer, montamine (15), showed significant in vitro anticolon cancer activity (IC₅₀=43.9 μM) while that of the monomer, moschamine (13), was of a moderate level (IC₅₀=81.0 μM).     

Cyclooxygenase-2 enzyme inhibitory withanolides from Withania somnifera leaves

Four novel withanolide glycosides and a withanolide have been isolated from the leaves of Withania somnifera. The structures of the novel compounds were elucidated as physagulin D (1→6)-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside (1), 27-O-β-d-glucopyranosyl physagulin D (2), 27-O-β-d-glucopyranosyl viscosalactone B (3), 4,16-dihydroxy-5β, 6β-epoxyphysagulin D (4), and 4-(1-hydroxy-2,2-dimethylcyclo-propanone)-2,3-dihydrowithaferin A (5) on the basis of 1D-, 2D NMR and MS spectral data. In addition, seven known withanolides withaferin A (6), 2,3-dihydrowithaferin A (7), viscosalactone B (8), 27-desoxy-24,25-dihydrowithaferin A (9), sitoindoside IX (10), physagulin D (11), and withanoside IV (12) were isolated. These withanolides were assayed to determine their ability to inhibit cycloxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes and lipid peroxidation. The withanolides tested, except compound 9, showed selective COX-2 enzyme inhibition ranging from 9 to 40% at 100 μg/ml. Compounds 4, 10 and 11 also inhibited lipid peroxidation by 40, 44 and 55%, respectively. The inhibition of COX-2 enzyme by withanolides is reported here for the first time.     

Proanthocyanidin glycosides from the leaves of Quercus ilex L. (Fagaceae)

From the polar extracts of the leaves of Quercus ilex L., two new proanthocyanidin glycosides, namely afzelechin-(4α→8)-catechin-3-O-β-glucopyranoside (1) and afzelechin-(4α→8)-catechin-3-O-α-rhamnopyranoside (2), were isolated in addition to catechin (3), proanthocyanidin B₃ (4), prodelphinidin C (5), dehydrodicatechin A (6), quercetin (7) and six known flavonol glucosides with their acylated derivatives (8-13) and ellagic acid (14). The structures of all isolated compounds were established by spectroscopic means, mainly 1D and 2D NMR, as well as LC/MS and HR-MS spectrometric analyses. The absolute configuration of compound 1 was determined by CD measurements. The proanthocyanidin glycosides are especially interesting, as they possess the sugar in the upper unit of the dimer, which is rare for this type of compounds.     

Bioactive meroditerpenes and indole alkaloids from the soil fungus Neosartorya fischeri (KUFC 6344), and the marine-derived fungi Neosartorya laciniosa (KUFC 7896) and Neosartorya tsunodae (KUFC 9213)

Two new metabolites including a new aszonalenin analogue (1c) and a new meroditerpene (3) were isolated, together with aszonalenin (1a), acetylaszonalenin (1b), 13-oxofumitremorgin B (2), aszonapyrone A (4b) and helvolic acid, from the culture of the soil fungus Neosartorya fischeri (KUFC 6344). While the ethyl acetate extract of the culture of the diseased coral-derived fungus Neosartorya laciniosa (KUFC 7896) furnished aszonapyrone B (4a), aszonapyrone A (4b), tryptoquivaline L and 3′-(4-oxoquinazolin-3-yl) spiro[1H-indole-3,5′-oxolane]-2,2′-dione, the ethyl acetate extract of the culture of the marine sponge-associated fungus Neosartorya tsunodae (KUFC 9213) yielded a new analogue of chevalone C (5) and helvolic acid. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis as well as HR-ESIMS. Compounds 1a–c, 2, 3, 4a, 4b and 5 were evaluated for their in vitro growth inhibitory activity on the MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma) cell lines by the protein binding dye SRB method.     

New pyridoacridine alkaloids from the purple morph of the ascidian Cystodytes dellechiajei

Two new pyridoacridine alkaloids, 13-didemethylaminocycloshermilamine D (1) and demethyldeoxyamphimedine (2), were isolated from the purple chromotype of the Western Mediterranean ascidian Cystodytes dellechiajei. This morph also contained the known shermilamine B (3), kuanoniamine D (4), N-deacetylshermilamine B (5), N-deacetylkuanoniamine D (6), styelsamines C (7), and D (8). The structures of new compounds were elucidated on the basis of spectroscopic data. A hypothetic biosynthetic pathway from the tetracyclic styelsamine D (8) was proposed for both compounds 1 and 2 and their antimicrobial potential was evaluated.     

Structural and stereochemical investigations into bromotyrosine-derived metabolites from southern Australian marine sponges, Pseudoceratina spp.

Chemical investigation of a southern Australian sponge, Pseudoceratina sp., resulted in the isolation of twelve bromotyrosine-derived alkaloids, comprising four new metabolites, aplysamine-7 (1), (−)-purealin B (2), purealin C (3) and purealin D (4); two new spiroisoxazole enantiomers, (−)-purealidin R (5) and (−)-aerophobin-2 (6); five known metabolites (−)-pseudoceratinine A (7), (−)-aeroplysinin-1 (8), aplysamine-2 (9), purpuramine G (10) and purpuramine J (11); and an artifact 12 derived from ethanolysis of 5. Structures for 1-12 were assigned on the basis of detailed spectroscopic analysis. A second southern Australian Pseudoceratina sp. afforded the first recorded account of a racemic bromotyrosine-derived spiroisoxazole, (±)-purealin (13b), together with the known achiral precursor purealidin A (15). A literature review of marine bromotyrosine-derived spiroisoxazoles reaffirmed the published dominance of (+)-spiroisoxazoles, acknowledging several accounts of (−)-spiroisoxazoles, while also revealing a wide range of chiroptical measurements suggestive of variable optical purity. The Pseudoceratina sp. metabolites 1-12, 13b and 15 were assessed for antibiotic properties, with the new metabolites 3 and 13b exhibiting broad spectrum activity against several Gram-positive bacteria.     

Cytotoxic dimeric sesquiterpenoids from Curcuma parviflora: isolation of three new parviflorenes and absolute stereochemistry of parviflorenes A, B, D, F, and G

Three novel dimeric sesquiterpenoids, named parviflorenes G-I (1-3), have been isolated from Curcuma parviflora (Zingiberaceae), and their structures were elucidated by means of spectroscopic studies. Absolute stereochemistry of parviflorene G (1) as well as previously isolated related compounds, parviflorenes A (4), B (5), D (6), and F (7), was revealed by CD spectral data and chemical means. Parviflorenes G (1) and I (3) were cytotoxic against HeLa cells, while parviflorenes A (4) and F (7) were cytotoxic against all tested tumor cell lines in the human cancer cell line panel assay.     

New polyesters from Talaromyces flavus

Six new polyesters, talapolyesters A–F (1–4, 14, and 16), together with 11 known ones 15G256ν (5), 15G256ν-me (6), 15G256π (7), 15G256β-2 (8), 15G256α-2 (9), 15G256α-2-me (10), 15G256ι (11), 15G256β (12), 15G256α (13), 15G256α-1 (15), and 15G256ω (17), were isolated from the wetland soil-derived fungus Talaromyces flavus BYD07-13, and their structures were determined by NMR and MS spectroscopic data. Among them, 1–4 and 16 were assembled in a different manner from that of the known 256 polyesters. All the polyesters are composed of (R)-2,4-dihydroxy-6-(2-hydroxypropyl)benzoic acid and (R)-3-hydroxybutyric acid/(S)-3,4-dihydroxybutyric acid residues. The absolute configurations of the residues were determined by alkaline hydrolysis. The cytotoxicity against five tumor cell lines of these compounds was examined, and a tight structure–activity relationship is proposed.     

Excavatoids A-D, new polyoxygenated briaranes from the octocoral Briareum excavatum

Three polyoxygenated briaranes, including two new compounds, excavatoids A (1) and B (2), and a known metabolite, briaexcavatin I (3), were isolated from the cultured octocoral Briareum excavatum. Moreover, the wild type B. excavatum, collected off southern Taiwan coast, yielded two new 5,6-epoxybriaranes, excavatoids C (4) and D (5). The structures of new compounds 1, 2, 4, and 5 were determined by spectroscopic methods and the structure of 1 was further confirmed by X-ray diffraction data analysis. The X-ray structure for briaexcavatin I (3) was also reported for the first time. Excavatoid A (1) is the first briarane which possesses six hydroxy groups and a 17-methoxy group. Excavatoid C (4) is the first 12,13-secobriarane which possesses a novel pentacyclic skeleton with an ?-lactone. Excavatoid D (5) displayed moderate inhibitory effects on superoxide anion generation and elastase release by human neutrophils.     

New phlegmarane-type, cernuane-type, and quinolizidine alkaloids from two species of Lycopodium

Two new phlegmarane-type alkaloids, cermizines A (1) and B (2), three new quinolizidine alkaloids, cermizine C (3) and senepodines G (4) and H (5), and a new C₁₆N₂ type alkaloid consisting of a quinolizidine and a piperidine ring, cermizine D (6), as well as two new cernuane-type alkaloids, cernuine N-oxide (7) and lycocernuine N-oxide (8), have been isolated together with cernuine (9) and lycocernuine (10) from the club moss Lycopodium cernuum and L. chinense. The relative stereochemistry of 1-4 and 6, and the absolute stereochemistry of 5, 7, and 8 were elucidated by combination of NOESY correlations, modified Mosher's method, chemical transformations, and computational methods. Cermizine D (6) might be a biosynthetic intermediate of cernuane-type alkaloids such as 7-10.     

New silatranes possessing urea functionality: Synthesis, characterization and their structural aspects

The present work aims at the synthesis of various novel silatranes bearing substituted urea functionality. Nucleophilic addition of various amines (morpholine, aniline, ethylenediamine and 3-aminopropyltriethoxysilane) to 3-isocyanatopropyltriethoxysilane resulted in the four triethoxysilanes; N-[3-(triethoxysilyl)propyl]morpholine-4-carboxylic acid amide (1), 1-[3-(triethoxysilyl)propyl]-3-phenylurea (2), 1,2-bis{N′-[3-(triethoxysilyl)propyl]ureido}-ethane (3) and N-[3-(triethoxysilyl)propyl]-N′-[3-(triethoxysilyl)propyl]urea (4), respectively. In the presence of a base the resulting silanes undergo transesterification reaction with triethanolamine, thus forming the corresponding silatranes, N-(3-silatranylpropyl)morpholine-4-carboxylic acid amide (5), 1-(3-silatranylpropyl)-3-phenylurea (6), 1,2-Bis[N′-(3-silatranylpropyl)ureido]-ethane (7) and N-(3-silatranylpropyl)-N′-(3-silatranylpropyl)urea (8), respectively. Among these are four novel compounds (5-8), which were characterized by elemental analysis, IR, multinuclear (¹H, ¹³C and ²⁹Si) NMR and mass spectroscopy. Structures of compounds 5 and 6 were deduced by X-ray crystallography. Single crystal X-ray studies revealed distorted trigonal bipyramidal coordination about Si in 5 and 6 with Si-N bond distance of 2.121(1) Å and 2.189(2) Å, respectively.     

New norditerpenoids from Cespitularia hypotentaculata

Four new norditerpenoids, designated as cespihypotins A (1), B (2), C (3) and D (4), were isolated from Cespitularia hypotentaculata Roxas (Xeniidae) that was collected in Taiwan. Compounds 1 and 2 are unprecedented structures having 13- and 14-membered lactone ring, respectively. Their structures were elucidated on the basis of extensive spectroscopic analysis. A plausible biogenetic pathway for compounds 1-4 was also proposed.     

Synthesis, conformation and PKC isozyme surrogate binding of indolinelactam-Vs, new conformationally restricted analogues of (−)-indolactam-V

New conformationally restricted analogues of tumor promoter (−)-indolactam-V (1), indolinelactam-Vs (8, 11) and their hexyl derivatives at position 1 or 7 (9, 10, 12, 13), were synthesized from 1. (3R)-Indolinelactam-V (8) adopted a conformation similar to the twist form of 1 with a cis amide, while the conformation of (3S)-indolinelactam-V (11) was close to that of the sofa form of 1 with a trans amide. 7-Hexyl derivatives of 8 and 11 (10, 13) showed binding affinities for C1 domains of protein kinase C (PKC) isozymes compared to 1, but exhibited little selectivity among these PKC isozymes. However, introduction of the hexyl group at position 1 of 8 and 11 significantly enhanced their binding selectivity for novel PKC isozymes. The best selectivity for novel PKC isozymes was observed in (3S)-1-hexylindolinelactam-V (12) with a sofa-like conformation. These results suggest that a sofa-restricted analogue of 1 with a hydrophobic chain at an appropriate position would be a promising lead for designing agents with a high selectivity for novel PKC isozymes.     

Endoplasmic reticulum (ER) stress protecting compounds from the mushroom Mycoleptodonoides aitchisonii

Two novel compounds, 3-(hydroxymethyl)-4-methylfuran-2(5H)-one (1) and (3R,4S,1′R)-3-(1′-hydroxyethyl)-4-methyldihydrofuran-2(3H)-one (2), were isolated along with two known ones (3 and 4) from an edible mushroom Mycoleptodonoides aitchisonii. The structures of 1-4 were determined by the interpretation of spectroscopic data. Compounds 1-4 showed protective activity against endoplasmic reticulum (ER) stress-dependent cell death.     

Isolation, structure elucidation and bioactivity of schischkiniin, a unique indole alkaloid from the seeds of Centaurea schischkinii

Reversed-phase HPLC analysis of the methanol extract of the seeds of Centaurea schischkinii afforded a novel indole alkaloid, named schischkiniin (1), together with four lignans, arctiin (2), matairesinoside (3), matairesinol (4), and arctigenin (5), and three flavonoids, astragalin (6), afzelin (7) and apigenin (8). While the structure of schiskiniin (1) was established unequivocally by UV, HRFABMS and a series of 1D and 2D NMR analyses, all known compounds were readily identified by comparison of their spectroscopic data with literature data. The free radical scavenging properties of these compounds were assessed using the DPPH assay, and their general toxicity and cytotoxicity were evaluated, respectively, by brine shrimp lethality and MTT cytotoxicity assays with CaCo-2 colon cancer cell lines. Arctigenin (5) exhibited promising in vitro anticancer activity (IC₅₀=7 μM) while with schischkiniin (1) the activity was of moderate level (IC₅₀=76 μM).     

Novel cyclopropyl diketones and 14-membered macrolides from the soil fungus Hamigera avellanea BCC 17816

Two novel cyclopropyl diketones, hamavellone A (1) and B (2), and two new 14-membered nonaketide macrolactones, hamigeromycin A (3) and B (4), together with six known compounds, 89-250904-F1 (radicicol analogue A, 5), pseurotin A (6), emodin (7), ω-hydroxyemodin (8), and emodin bianthrones (9 and 10) were isolated from the soil fungus Hamigera avellanea BCC 17816. The structures of the new compounds were defined by analysis of NMR and MS data. The absolute stereochemistry of 3 was addressed by chemical correlation to 5. Hamavellone B (2) exhibited antimalarial activity with an IC₅₀ of 5.2 μg/mL, whereas it also showed comparable cytotoxicity.     

Novel taxoids from the Chinese yew Taxus yunnanensis

Six new taxoids, taxuyunnanines W (1), X (2), Y (3), Z (5), 10-deacetyl-10-(β-glucopyranosyl)-yunnanxane (8), and 7-(β-xylosyl)-N-methyl-taxol C (10), as well as taxuchin B (4) and yunnanxane (7), have been isolated from the bark of Taxus yunnanensis. Compounds 1 and 2 were characterized as 11(15→1)-abeo taxoids containing an orthoester group, which have not been reported from any Taxus plants to date; isolates 3 and 5 are the examples of taxanes having a tetrahydronfuran ring, being reported only for the second time; and 8 is the first natural 6/8/6 skeletal type taxane glucosidic form. This is also the first report of a co-occurrence of xylosidation and N-methylation in a taxane (10). Compound 4 is the only known chlorine-containing taxane found in nature thus far, and is being reported from this plant for the first time. The structures were determined by spectroscopic and chemical means including 1D and 2D NMR spectra.     

Syntheses, crystal structures and properties of Co(II) complexes with N,N′-bis(3-pyridylmethyl)-1,4-benzenedimethyleneimine (bpb), and Cd(II), Hg(II) complexes with reduced bpb

Five novel coordination polymers, [Co(bpb)₂Cl₂] (1), [Co(bpb)₂(SCN)₂] (2), [Cd(H₄bpb)_0.5(dmf)(NO₃)₂] (3), [Cd₂(H₄bpb)Br₄] (4), and [Hg₂(H₄bpb)I₄] (5) [bpb=N,N′-bis(3-pyridylmethyl)-1,4-benzenedimethyleneimine, H₄bpb=N,N′-bis(3-pyridylmethyl)-1,4-benzenedimethylamine], were synthesized and their structures were determined by X-ray crystallography. In the solid state, complex 1 is a 1D hinged chain, while 2 has 2D network structure with the ligand bpb serving as a bridging ligand using its two pyridyl N atoms. The imine N atoms keep free of coordination and bpb acts as a bidentate ligand in both 1 and 2. Complexes 3, 4, and 5 with reduced bpb ligand, i.e. H₄bpb, show similar 2D network structure, in which ligand H₄bpb serves as a tetradentate ligand. Thermogravimetric analyses for complexes 1-5 were carried out and found that they have high thermal stability. The magnetic susceptibilities of compounds 1, 2 were measured over a temperature range of 75-300 K.     

Three new diterpenoids, tricalysiolide H and tricalysiones A and B, from Tricalysia dubia

Three new diterpenoids, tricalysiolide H (1) and tricalysiones A (2) and B (3), with novel structural features were isolated from the wood of Tricalysia dubia, together with a known compound, cafestol (4). The structures of 1-3 were elucidated on the basis of 2D NMR spectroscopy and X-ray crystallographic analysis.     

Bisleuconins A-D: a pair of epimeric ent-kauranoid dimers and two new asymmetric analogues isolated from Isodonleucophyllus

A phytochemical investigation of Isodon leucophyllus led to the isolation of four novel ent-kauranoid dimers: bisleuconins A-D (1-4), and one known compound, rabdoloxin A (5). It was interesting that the structures of bisleuconins A (1) and B (2) were elucidated as a pair of epimeric ent-kauranoid dimers with unique linkage pattern C-16→C-17′ to connect two monomers. Bisleuconins C (3) and D (4) were two new asymmetric ent-kauranoid dimers. A possible biogenetic pathway of 1 and 2 was also proposed.