lignans and conidendrin

α-Conidendrin is a lignan isolated from Taxus wallichiana and other species. In the present study, we demonstrated that α-conidendrin inhibited the cell-surface expression of intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor-α (TNF-α) at an IC

Topics: A549 Cells; Adenocarcinoma of Lung; Cell Survival; Chromans; Cyclooxygenase 2; E-Selectin; Human Umbilical Vein Endothelial Cells; Humans; Intercellular Adhesion Molecule-1; Lignans; Lung Neoplasms; Promoter Regions, Genetic; Signal Transduction; Tetrahydronaphthalenes; Transcription Factor RelA; Tumor Necrosis Factor-alpha

α-Conidendrin is a polyphenolic compound found mainly in Taxus yunnanensis, as the source of chemotherapy drug paclitaxel, which has been used in traditional medicine for treatment of cancer. This study aimed to investigate the anticancer activity and molecular mechanisms of α-conidendrin on breast cancer cell lines. The results of the present study show that α-conidendrin possesses potent antiproliferative effects on breast cancer cell lines MCF-7 and MDA-MB-231. α-Conidendrin significantly induced apoptosis in breast cancer cells via reactive oxygen species generation, upregulation of p53 and Bax, downregulation of Bcl-2, depolarization of mitochondrial membrane potential (MMP), release of cytochrome c from mitochondria, and activation of caspases-3 and -9. α-Conidendrin remarkably inhibited the proliferation of breast cancer cells through induction of cell cycle arrest by upregulating p53 and p21 and downregulating cyclin D1 and CDK4. Unlike breast cancer cells, the antiproliferative effect of α-conidendrin on human foreskin fibroblast cells (normal cells) was very small. In normal cells, reactive oxygen species levels, loss of MMP, release of cytochrome c, mRNA expression of p53, p21, cyclin D1, CDK4, Bax, and Bcl-2 as well as mRNA expression and activity of caspases-3 and -9 were significantly less affected by α-conidendrin compared with cancer cells. These results suggest that α-conidendrin can be a promising agent for treatment of breast cancer with little or no toxicity against normal cells.

Topics: Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Humans; Lignans; Taxus; Tetrahydronaphthalenes

All eight stereoisomers of conidendrin were synthesized from (1 

Topics: Chemistry Techniques, Synthetic; Hydrolysis; Kinetics; Lignans; Stereoisomerism; Tetrahydronaphthalenes

The lignan 7'-hydroxymatairesinol (1), extracted from the knotwoods of fir (Abies alba), spruce (Picea abies), and Douglas fir (Pseudotsuga menziesii), exhibited unexpected reactivity when esterification reactions were attempted on the hydroxy group at position C-7'. To circumvent the rapid intramolecular cyclization procedure, leading quantitatively to the lignan conidendrin (7), a simple strategy for 7'-esterification of 1 under mild conditions (three steps, up to 80% overall yield) was developed. Compared to hydroxymatairesinol (1) (log K'

Topics: alpha-Tocopherol; Antioxidants; Biphenyl Compounds; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Picea; Picrates; Pinus; Stereoisomerism; Tetrahydronaphthalenes

Molecular dynamics (MD) simulations were performed on sterically hindered α-conidendrin-based chiral 1,4-diols (LIGNOLs) from the naturally occurring lignan hydroxymatairesinol (HMR) using the GROMACS software. The aim of this study was to explore the conformational behaviour of the LIGNOLs in aqueous solution adopting the TIP4P model. The topologies of the LIGNOLs were constructed manually and they were modeled with the OPLS-AA force field implemented in GROMACS. The four most relevant torsional angles in the LIGNOLs were properly analyzed during the simulations. The determining property for the conformation preferred in aqueous solution was found to be the lowest energy in gas phase. The solvation effects on the LIGNOLs were also studied by quantum chemical calculations applying the COnductor-like Screening MOdel (COSMO). The hydration studies of the MD simulations showed that several of these LIGNOLs, produced from a renewable source, have a great potential of acting as chiral catalysts.

Topics: Lignans; Models, Molecular; Molecular Conformation; Molecular Dynamics Simulation; Software; Tetrahydronaphthalenes

From the aqueous extract of the wood of Taxus yunnanensis, which showed cytochrome P450 3A4 (CYP3A4) inhibition, a new isoflavan [(3S,4R)-4'-hydroxy-6,3'-dimethoxyisoflavan-4-ol (1)], a new degraded lignan [2,3-bis(hydroxymethyl)-7-hydroxy-6-methoxy-1-tetralone (2)], and a new lignan [(7R)-7-hydroxytaxiresinol (3)] were isolated, together with nine known lignans. Among the isolates obtained, α-conidendrin (12) showed strong CYP3A4 inhibition with an IC(50) value of 0.2 μM.

Topics: Antineoplastic Agents, Phytogenic; Antioxidants; Biphenyl Compounds; Colletotrichum; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Screening Assays, Antitumor; Free Radical Scavengers; Furans; Hep G2 Cells; Humans; Isocoumarins; Isoflavones; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Picrates; Taxus; Tetrahydronaphthalenes; Wood

An efficient domino cyclization method for the construction of aza-podophyllotoxin/aza-conidendrin derivatives has been established. Reactions of different dienes with aryl halides in the presence of a palladium catalytic system produced different kinds of podophyllotoxin derivatives through a highly regioselective C-H functionalization. Treatment of dienes with aryl halides that have electron-withdrawing substituents on the phenyl ring created aza-podophyllotoxin derivatives by means of the functionalization of the C-H bonds ortho to the C-halide bonds of the incoming aryl halides. The reaction of dienes with 1-iodobenzene or aryl halides that incorporate electron-donating groups produced aza-conidendrin derivatives by means of the functionalization of both sp(3) C-H and sp(2) C-H bonds. The regioselective C-H functionalization for the formation of different pseudo-podophyllotoxin/-conidendrin derivatives is proven by analyses of the (1)H NMR spectra of the products and selective X-ray analyses of the structures of the products. Thus, the palladium-catalyzed domino cyclization of 1,6-dienes for the preparation of aza-podophyllotoxin/aza-conidendrin derivatives can be controlled by selectively controlling the C-H functionalization.

Topics: Aza Compounds; Crystallography, X-Ray; Cyclization; Lignans; Models, Molecular; Molecular Conformation; Podophyllotoxin; Tetrahydronaphthalenes

[reaction: see text] Total syntheses of seven biologically important lignan natural products, including (-)-arctigenin, (-)-matairesinol, and (-)-alpha-conidendrin, by way of a highly stereoselective domino radical sequence is presented. The reported stereochemistry of the natural product 7-hydroxyarctigenin is shown to be erroneous; a diastereoisomeric structure is assigned to the natural product.

Topics: Antineoplastic Agents; Antiviral Agents; Biological Products; Free Radicals; Furans; HL-60 Cells; Humans; Lignans; Molecular Structure; Stereoisomerism; Tetrahydronaphthalenes

Oxidation of alpha-conidendrin (3) by Fremy's salt favored formation of an o-quinone (4) at the pendant aromatic ring as opposed to the fused aromatic ring. Quinone reduction and phenolic methylation, followed by lactone reduction, and subsequent oxidation by dichlorodicyanoquinone produced sikkimotoxin oxabicyclooctane (7), while oxidation with cupric sulfate/potassium persulfate gave sikkimotoxin dioxatricyclodecane (8).

Topics: Catalysis; Indicators and Reagents; Lignans; Oxidation-Reduction; Podophyllotoxin; Quinones; Structure-Activity Relationship; Tetrahydronaphthalenes

Derivatives of alpha-conidendrin, podophyllotoxin, and sikkimotoxin were prepared to evaluate the cytotoxic contributions of C-4 configuration and pendant and fused arene substitutions. Dimethyl-alpha-conidendryl alcohol (5), 9-deoxypodophyllol (6), and 9-deoxysikkimol (17) were dehydrated to their respective oxolane derivatives 4, 3, and 9. Diols 5 and 6 were converted via oxabicyclo[3.2.1]octanols 10 and 14 to target oxolanes 8 and 7 where C-4 had been inverted relative to that in 3 and 4. Cytotoxicities of the five oxolanes were determined in two drug-sensitive human leukemia and two multidrug-resistant cell lines expressing P-glycoprotein or multidrug-resistance associated protein (MRP). Changing the pendant arene configuration or replacing a m-methoxy by hydrogen resulted in a 100-fold cytotoxicity loss. Replacing a methylenedioxy group in the fused arene by two methoxy substituents reduced cytotoxicity by 10-fold. Drug-resistant cell lines were equally resistant to compounds 3, 4, 8, and 9 indicating that these four compounds do not serve as substrates of the transport proteins P-glycoprotein and MRP.

Topics: Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP-Binding Cassette Transporters; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Lignans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Conformation; Multidrug Resistance-Associated Proteins; Podophyllotoxin; Structure-Activity Relationship; Tetrahydronaphthalenes; Tumor Cells, Cultured

Topics: Agrobacterium; Aldehydes; Benzaldehydes; Cellulose; Lignans; Lignin; Metabolism; Phenols; Research; Resins, Plant; Resins, Synthetic; Rhizobium; Soil Microbiology; Tetrahydronaphthalenes

Topics: Lignans; Lignin; Tetrahydronaphthalenes

Topics: Humans; Lignans; Naphthalenes; Tetrahydronaphthalenes

Topics: Carbohydrate Metabolism; Flavobacterium; Lignans; Lignin; Polysaccharides; Tetrahydronaphthalenes

Topics: Flavobacterium; Lignans; Lignin; Tetrahydronaphthalenes