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Lignans, phenylpropanoids and polyacetylenes from Chaerophyllum aureum L. (Apiaceae).

Sub-aerial parts of Chaerophyllum aureum L. yielded two polyacetylenes, falcarinol (1), falcarindiol (2), three lignans, namely nemerosin (3), deoxypodorhizone (4), deoxypodo-phyllotoxin (5), two phenylpropanoids, 1'-hydroxymyristicin (6) and its angeloyl ester (7). Compounds 6 and 7 were isolated for the first time from plant material and their structures were elucidated by means of extensive 1- and 2-dimensional NMR spectroscopy and high resolution mass spectrometry. In bioautographic tests on TLC plates the dichloromethane extract showed a significant antimicrobial activity. Falcarindiol was identified as the main active principle whereas the phenylpropanoids and lignans showed no activity.

Acetylene↗

Cytotoxic polyacetylenes from the marine sponge Petrosia sp.

Three C46 (1-3) and three C30 (4-6) polyacetylenic alcohols with cytotoxic activity against a small panel of human solid-tumor cell lines have been isolated from the marine sponge Petrosia sp. Although compound 1 was identified as the stereoisomer of petrocortyne A, the structures of compounds 2-5 have not been previously reported and were established by spectral methods. Compound 6 was identified as the known compound petrosiacetylene D. The stereochemistry of compounds 1-5 was determined by the modified Mosher's method.

Acetylene↗

New cytotoxic polyacetylenes from the marine sponge Petrosia.

New polyacetylenic alcohols with a C(45) carbon skeleton (2) and with an enone moiety in the alkyl chain (C(46), 1) were isolated from the marine sponge Petrosia sp. The gross structures of 1 and 2 were established by spectral methods, and the absolute stereochemistry was determined by the modified Mosher's method. Compounds 1 and 2 displayed considerable cytotoxicity against a small panel of human solid tumor cell lines. Significant inhibitions on DNA replication by 1 and 2 were also observed which could be explanative of their cytotoxicity.

Acetylene↗

Highly stable vesicles composed of a new chain-terminus acetylenic photopolymeric phospholipid.

Stability, ease of production, and storage convenience were addressed for polymerized vesicles composed of 1,2-bis(trideca-12-ynoyl)-sn-glycero-3-phosphocholine. The following vesicle properties were investigated before and after polymerization: size, shape, lamellarity, dispersity, degree of polymerization, membrane fluidity, and structural stability. A fairly monodisperse, unilamellar sub-micron vesicle suspension undergoes nearly complete polymerization of the chain-terminus acetylenic to polyacetylenic conversion as monitored by Fourier transform infrared spectroscopy. (1)H nuclear magnetic resonance spectroscopy and thin layer chromatography provide additional evidence for extensive lipid polymerization. Using differential scanning calorimetry, a gel/liquid transition was not observed for either polymerized or non-polymerized vesicles within the temperature range of 5-65 degrees C. These polymerized vesicles remained structurally stable and suspended for months at room temperature. However, vesicle size did decrease with increasing degree of polymerization. Polymerized vesicles remained spherical but decreased in size by 15% when subjected to 52 wt.% aqueous ethanol and did not change significantly in size and dispersity after a freeze-dry/resuspend cycle.

Alkynes↗

Effect of polyacetylenes on the neurite outgrowth of neuronal culture cells and scopolamine-induced memory impairment in mice.

Polyacetylenic alcohols and their linoleates isolated from Panax ginseng C. A. MEYER and Cirsium japonicum DC., of which the lipophilic extracts had been found to affect the neuritogenesis of cultured paraneurons, were demonstrated to have a significant neuritogenic effect on PC12h and Neuro2a cells. Panaxynol and the acetylenic triol in particular were highly efficient at concentrations > or = 2 microm. Panaxynol (20 mg/kg/d, i.p., for 3 d) was confirmed to improve scopolamine-induced memory deficit in mice (Y-maze task). It is suggested that the promotion of neuritogenesis in cultured paraneurons by the addition of panaxynol is related its ability to improve memory deficits in animals.

Acetylene↗

Inhibition of NF-kappaB activation and expression of inflammatory mediators by polyacetylene spiroketals from Plagius flosculosus.

Transcription factor NF-kappaB plays a key role for the inducible expression of genes mediating proinflammatory effects and is thus an important target for the development of antiinflammatory drugs. Here, we show that extracts from the plant Plagius flosculosus (L.) Alavi and Heyw. can inhibit the induction of NF-kappaB activity, and we describe the identification of three spiroketal compounds. Of those, only compound 1 could inhibit the phosphorylation and proteasomal degradation of IkappaB, thus preventing the nuclear import and DNA binding of NF-kappaB. Accordingly, compound 1, which is also found in the widely used medicinal herb chamomile, interfered with the LPS-induced production of IL-1, IL-6, TNF, and PGE2 in primary human monocytes.

Acetylene↗

Lembehyne A, a spongean polyacetylene, induces neuronal differentiation in neuroblastoma cell.

Lembehyne A (LB-A), a spongean polyacetylene, induced neuronal cell differentiation in a neuroblastoma cell line, Neuro 2A. The LB-A treatment of Neuro 2A cells predominantly resulted in a morphological change with bipolar neurites. The acetylcholinesterase activity of Neuro 2A was also increased by the treatment of LB-A. Furthermore, the cell cycle of Neuro 2A cells was found to be specifically blocked at the G1 phase by LB-A. The structure-activity relationship study using the LB-A analogues revealed the importance of the terminal 1-yn-3-ol and unsaturated long-chain alkyl moieties for the neuronal differentiation activity of LB-A.

Acetylcholinesterase↗

Gymnasterkoreaynes A-F, cytotoxic polyacetylenes from Gymnaster koraiensis.

Six new polyacetylenes, gymnasterkoreaynes A-F (1-6), were isolated from the roots of Gymnaster koraiensis, together with 2,9,16-heptadecatrien-4,6-diyn-8-ol (7) and 1,9,16-heptadecatriene-4,6-diyn-3,8-diol (8), by bioassay-guided fractionation using the L1210 tumor cell line as a model for cytotoxicity. The structures of compounds 1-6 were established spectroscopically, which included 2D NMR experiments. Gymnasterkoreaynes A-F (1-6) are linear diacetylenes and are structurally related to falcarinol, panaxynol, panaxydiol, and panaxytriol. Of the compounds isolated, gymnasterkoreaynes B (2), C (3), F (6), and 1,9,16-heptadecatrien-4,6-diyn-3,8-diol (8) exhibited significant cytotoxicity against L1210 tumor cells with ED(50) values of 0.12-3.3 microg/mL.

Acetylene↗

Energy and electron transfer in polyacetylene-linked zinc-porphyrin-[60]fullerene molecular wires.

The synthesis and electrochemical and photophysical studies of a series of alkyne-linked zinc-porphyrin-[60]fullerene dyads are described. These dyads represent a new class of fully conjugated donor-acceptor systems. An alkynyl-fullerene synthon was synthesized by a nucleophilic addition reaction, and was then oxidatively coupled with a series of alkynyl tetra-aryl zinc-porphyrins with 1-3 alkyne units. Cyclic and differential pulse voltammetry studies confirmed that the porphyrin and fullerene are electronically coupled and that the degree of electronic interaction decreases with increasing length of the alkyne bridge. In toluene, energy transfer from the excited zinc-porphyrin singlet to the fullerene moiety occurs, affording fullerene triplet quantum yields of greater than 90 %. These dyads exhibit very rapid photoinduced electron transfer in tetrahydrofuran (THF) and benzonitrile (PhCN), which is consistent with normal Marcus behavior. Slower rates for charge recombination in THF versus PhCN clearly indicate that charge-recombination events are occurring in the Marcus inverted region. Exceptionally small attenuation factors (beta) of 0.06+/-0.005 A(-1) demonstrate that the triple bond is an effective mediator of electronic interaction in zinc-porphyrin-alkyne-fullerene molecular wires.

Acetylene↗

Antiallergic agents from natural sources. 3. Structures and inhibitory effects on nitric oxide production and histamine release of five novel polyacetylene glucosides from Bidens parviflora WILLD.

Five new polyacetylene glucosides, bidensyneosides A1, A2, B, C (1-4), and 3-deoxybidensyneoside B (5), have been isolated from the air-dried whole plant of Bidens parviflora WILLD. The structures were identified based on spectroscopic analysis, physicochemical properties, and application of the modified Mosher method to be 3(R),8(E)-8-decene-4,6-diyne-1,3-diol 1-O-beta-D-glucopyranoside (1), deca-3(R),8(Z) 8-decene-4,6-diyne-1,3-diol 1-O-beta-D-glucopyranoside (2), 3(R)-deca-4,6,8-triyne-1,3-diol 1-O-beta-D-glucopyranoside (3), 3(R),8(E)-8-decene-4,6-diyne-1,3,10-triol 1-O-beta-D-glucopyranoside (4), and 8(E)-8-decene-4,6-diyne-1,10-diol 1-O-beta-D-glucopyranoside (5), respectively. These compounds inhibited nitric oxide (NO) production in lipopolysaccharide and interferon-gamma activated murine macrophages (RAW264.7) and also inhibited histamine release from rat mast cells stimulated by the antigen-antibody reaction.

Acetylene↗

Suppression of U937 human monocytic leukemia cell growth by dideoxypetrosynol A, a polyacetylene from the sponge Petrosia sp., via induction of Cdk inhibitor p16 and down-regulation of pRB phosphorylation.

Dideoxypetrosynol A, a polyacetylene from the marine sponge Petrosia sp., is known to exhibit significant selective cytotoxic activity against a small panel of human tumor cell lines, the mechanisms of which however, are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which dideoxypetrosynol A exerts its anti-proliferative action in cultured human monocytic leukemia U937 cells. We observed that the proliferation-inhibitory effect of dideoxypetrosynol A was due to the induction of G1 arrest in the cell cycle, the effects of which were associated with up-regulation of cyclin D1 and down-regulation of cyclin E, in a concentration-dependent manner without any change in cyclin-dependent-kinases (Cdks) expression. Dideoxypetrosynol A markedly induced the levels of Cdk inhibitor p16/INK4a expression. Furthermore, down-regulation of phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and transcription factor E2F-1. Overall, our results demonstrate a combined mechanism involving the inhibition of pRB phosphorylation and induction of p16 as targets for dideoxypetrosynol A, may explain some of its anti-cancer effects.

Acetylene↗

Two formation regions for Titan's hazes: indirect clues and possible synthesis mechanisms.

It is suggested that aerosol particles forming the detached and main haze layers of Titan's atmosphere do not originate in the same atmospheric levels. Particles present above approximately 350 km could be formed of polyacetylenes synthetized in the 500-800 km altitude range through successive insertion reactions involving the C2H radical under the action of solar ultraviolet photons (Yung et al., Astrophys. J. Suppl. 55, 465, 1984). They might contain C-N oligomers in comparable amounts, as well as C-H-N oligomers synthetized at high altitude (900-1000 km) by the action of suprathermal Saturn plasma electrons. Physically, they are expected to consist of fluffy aggregates of density approximately 0.01-0.1 g cm-3. Their mass production rate is small (10(-15)-10(-14) kg m-2 s-1), that is typically 10% or less of the main haze production rate. Due to their low fall velocity, they are very sensitive to large scale horizontal motions and one substantial part of them may be swept away by meridional circulation at the detached haze level. The altitude range where these aerosols are created is well above the range proposed by Cabane et al. (Planet. Space Sci. 41, 257, 1993) for aerosols of the main haze layer, on the basis of a new fractal microphysical modeling of Titan's aggregates, that is approximately 350-400 km. A natural outcome of this apparent discrepancy is to suppose that there is a second formation region, below approximately 400 km altitude, giving rise to the main haze layer. The aim of the present paper is to review the different possible formation mechanisms of this main haze layer and assess their ability to account for the observed characteristics of the haze. Several conditions are established. The first one, called "condition A", concerns the formation altitude range imposed by fractal modeling. Possible chemical and energy sources are examined. Two additional constraints, relative to the minimum gas mass ("condition B") and input energy ("condition C") required for efficient conversion of gas into aerosols, are defined. By comparing the production rates of the haze, as derived from microphysical models, and of gaseous chemical species, as derived from photochemical models, five possible source constituents are identified: N2, CH4, C2H2, C2H6 and HCN. Polymerization of C2H2 into (C2H2)n through action of solar ultraviolet photons is shown to be rather improbable (condition A is hardly satisfied). From both our current knowledge of the gaseous phase photochemistry, through modeling and laboratory experiments, and existing models of the interaction between Saturn magnetosphere and Titan atmosphere, the formation of C-H-N polymers through action of Saturn magnetospheric energetic particles (E approximately 100 keV), is proposed as the basic polymerization mechanism in the lower formation region (conditions A,B and C are jointly satisfied).

Acetylene↗

Immunosuppressive and anti-inflammatory effects of methanolic extract and the polyacetylene isolated from Bidens pilosa L.

The immunomodulatory effect of the methanolic extract obtained from dried leaves of Bidens pilosa L. (Asteraceae) and the polyacetylene 2-O-beta-D-glucosyltrideca-11 E-en-3,5,7,9-tetrayn-1,2-diol (PA-1) isolated from it was investigated. The extract inhibited the proliferative response in two in vitro models: human lymphocytes stimulated by 5 microg ml(-1) phytohemagglutinin (PHA) or to 100 nM 12-O-tetradecanoyl phorbol-13-acetate (TPA) plus 0.15 microM ionomycin and murine lymphocytes stimulated by 5 microg ml(-1) concanavalin A (Con A) or in the mixed leukocyte reaction (IC50 = 12.5 to 25 microg ml(-1)). PA-1 was 10-told more potent than the original extract in blocking both human and murine lymphocyte proliferation (IC50 = 1.25 to 2.5 microg ml(-1)). In mice, the intraperitoneal (i.p.) administration of methanolic extract of B. pilosa significantly reduced the size of the popliteal lymph node (PLN) after the inflammation induced by zymosan. One week after the injection of zymosan (150 microg) in the foot pad, PLN weighed 4.6 +/- 0.6 mg in comparison with 0.5 +/- 0.07 mg of the contralateral non-inflamed foot pad. The i.p. treatment with 10 mg extract from day 2 to day 6 after zymosan injection reduced the PLN weight to 1.8 +/- 0.3 mg. The data suggest an immunosuppressive activity of components of B. pilosa that may explain its popularly perceived anti-inflammatory effect.

Acetylene↗

In vitro anti-inflammatory and pro-aggregative effects of a lipid compound, petrocortyne A, from marine sponges.

(3 S,14 S)-Petrocortyne A, a lipid compound (a C(46) polyacetylenic alcohol), from marine sponges ( Petrosia sp.) is potently cytotoxic against several solid tumour cells. In this study, we investigated in vitro anti-inflammatory and pro-aggregative effects of petrocortyne A at non-cytotoxic concentrations on various cellular inflammatory phenomena using the macrophage and monocytic cell lines RAW264.7 and U937. Petrocortyne A blocked tumour necrosis factor-alpha (TNF-alpha) production strongly and concentration-dependently in lipopolysaccharide (LPS)-activated RAW264.7 cells and phorbol 12-myristate 13-acetate (PMA)/LPS-treated U937 cells. It also blocked NO production concentration-dependently in LPS- or interferon (IFN)-gamma-treated RAW264.7 cells. Among the migration factors tested, the compound selectively blocked the expression of hepatocyte growth factor/scatter factor (HGF/SF). On the other hand, as assessed by a cell-cell adhesion assay, petrocortyne A did not block the activation of adhesion molecules induced by aggregative antibodies to adhesion molecules, but suppressed PMA-induced cell-cell adhesion significantly. Intriguingly, petrocortyne A induced U937 homotypic aggregation following long exposure (2 and 3 days), accompanied by weak induction of pro-aggregative signals such as tyrosine phosphorylation of p132 and phosphorylation of extracellular signal-related kinase 1 and 2 (ERK 1/2). Petrocortyne A may thus inhibit cellular inflammatory processes and immune cell migration to inflamed tissue.

Acetylene↗