Aporphine alkaloids and lignans formed in response to injury of sapwood in Liriodendron tulipifera

Two new phenolic aporphine alkaloids, (+)-lirioferine and (+)liriotulipiferine, were isolated from discolored sapwood of L. tulipifera. Injury to the tree stem greatly stimulated biosynthesis of glaucine and phenolic alkaloids related to glaucine including thaliporphine, predicentrine, N-methylaurotetanine and corunine as well as the above two compounds. Injury also stimulated synthesis of oxoaporphine related and other polymeric pigments. Corunine was responsible for at least part of the color of discolored sapwood. None of the above compounds except glaucine was detected in normal sapwood or heartwood of L. tulipifera. Thus, formation of alkaloids and lignans in discolored sapwood differs both quantitatively and qualitatively from that observed during the normal transition of sapwood to heartwood in this tree. The compounds formed in response to injury differed substantially from one zone of injury to another within the same tree.     

Aporphine alkaloids of annona squamosa

The aporphine alkaloids anonaine, roemerine, norcorydine, corydine, norisocorydine, isocorydine and glaucine have been isolated from Annona squamosa.     

Aporphine alkaloids and lignans in heartwood of Liriodendron tulipifera

The following compounds were isolated from heartwood of Liriodendron tulipifera: glaucine, dehydroglaucine, asimilobine, N-acetylnornuciferine, norushinsunine, liriodenine, O-methylatheroline, (+)-syringaresinol, (+)-syringaresinol dimethyl ether and syringaldehyde. The occurrence of 1-benzyltetrahydroisoquinoline alkaloids also has been indicated by mass spectroscopy. Some characteristic spectral properties of these aporphine alkaloids and their probable biosynthetic pathways are discussed.     

Alkaloids of Litsaea laeta and L. salicifolia

The structure for laetine (2-hydroxy-1-methyl 10,11-methylenedioxy noraporphine), a new alkaloid from the bark of Litsaea laeta has been established. N,O-Dimethylharnovine and glaucine were also isolated from the same source. C-2 hydroxy aporphines are characteristic of L. laeta. Two known alkaloids, dicentrinone and nordicentrine, have also been isolated from the leaves of L. salicifolia.     

Effects of berberine,glaucine, stephaglabrine,and sanguirythrine on neuromuscular transmission

The effects of certain alkaloid (glaucine, stephaglabrine, and sanguirythrine) on parameters of neuromuscular transmission follow a complex pattern and are thought likely to operate via two or more different mechanisms. These alkaloids, in common with berberine, reduced the amplitude of miniature potentials at the frog neuromuscular junction. All four concentrations reduced and raised miniature potential rate at low and high concentrations respectively — a very marked action in the case of sanguirythrine, producing virtually a 100-fold increase, probably due to its uncoupling effect on oxidative phosphorylation at the mitochondria of the nerve endings. Sanguirythrine and stephaglabrine both gave rise to repeated muscular contraction which matches their anticholinesterase activity. High glaucine concentrations also induced contraction of the muscles.Institute for Hydrobiontic Substance Research, Soviet Ministry of Health, Moscow. Translated from Neirofiziologiya, Vol. 23, No. 2, pp. 131–135, March–April, 1991.     

Cinnamoyl- and hydroxycinnamoyl amides of glaucine and their antioxidative and antiviral activities

The aporphine alkaloid glaucine has been converted into 3-aminomethylglaucine and its free amino group has been linked to cinnamic, ferulic, sinapic, o-, and p-coumaric acids. The antioxidative potential of the synthesized amides was studied against DPPH(*) test. All of the tested compounds demonstrated higher radical scavenging activity than glaucine and 3-aminomethylglaucine, and lower antioxidative effect than the free hydroxycinnamic acids. The newly synthesized compounds were tested in vitro for antiviral activity against viruses belonging to different taxonomic groups.     

Structure-affinity relationships of halogenated predicentrine and glaucine derivatives at D1 and D2 dopaminergic receptors: halogenation and D1 receptor selectivity

Halogenation of the aporphine alkaloid boldine at the 3-position leads to increased affinity for rat brain D(1)-like dopaminergic receptors with some selectivity over D(2)-like receptors. A series of 3-halogenated and 3,8-dihalogenated (halogen=Cl, Br or I) derivatives of predicentrine (9-O-methylboldine) and glaucine (2,9-di-O-methylboldine) were prepared and assayed for binding at D(1) and D(2) sites. Halogenation of predicentrine led to strong increases in affinity for D(1)-like receptors, while the affinities for D(2)-like receptors were either practically unchanged or reduced three- to fourfold. Halogenated glaucine derivatives did not show any clear trend towards enhanced selectivity, and the affinities were poor and similar to or worse than the values previously recorded for glaucine itself. Together with earlier work on boldine derivatives, these results suggest that the 2-hydroxy group on the aporphine skeleton may determine a binding mode favoring D(1)-like over D(2)-like receptors, with enhanced affinity when the C-3 position is halogenated.     

Neuraminidase inhibitory activities of quaternary isoquinoline alkaloids from Corydalis turtschaninovii rhizome

Clostridium perfringens is a Gram-positive spore-forming bacterium that causes food poisoning. The neuraminidase (NA) protein of C. perfringens plays a pivotal role in bacterial proliferation and is considered a novel antibacterial drug target. Based on screens for novel NA inhibitors, a 95% EtOH extract of Corydalis turtschaninovii rhizome showed NA inhibitory activity (68% at 30 μg/ml), which resulted in the isolation of 10 isoquinoline alkaloids; namely, palmatine (1), berberine (2), coptisine (3), pseudodehydrocorydaline (4), jatrorrhizine (5), dehydrocorybulbine (6), pseudocoptisine (7), glaucine (8), corydaline (9) and tetrahydrocoptisine (10). Interestingly, seven quaternary isoquinoline alkaloids 1–7 (IC₅₀ = 12.8 ± 1.5 to 65.2 ± 4.5 μM) showed stronger NA inhibitory activity than the tertiary alkaloids 8–10. In addition, highly active compounds 1 and 2 showed reversible non-competitive behavior based on a kinetic study. Molecular docking simulations using the Autodock 4.2 software increased our understanding of receptor–ligand binding of these compounds. In addition, we demonstrated that compounds 1 and 2 suppressed bacterial growth.     

Identification and quantification of isoquinoline alkaloids in the genus Sarcocapnos by GC-MS

Six cularine alkaloids, cularicine, O-methylcularicine, celtisine, cularidine, cularine and celtine, three isocularine alkaloids, sarcophylline, sarcocapnine and sarcocapnidine, and five non-cularine alkaloids, glaucine, protopine, ribasine, dihydrosanguinarine and chelidonine, were identified and quantified by GC-MS in nine taxa of the genus Sarcocapnos (Fumariaceae). The chemotaxonomic significance of the results is discussed.     

Influence of combinations of digitonin with selected phenolics,terpenoids, and alkaloids on the expression and activity of P-glycoprotein in leukaemia and colon cancer cells

P-glycoprotein (P-gp or MDR1) is an ATP-binding cassette (ABC) transporter. It is involved in the efflux of several anticancer drugs, which leads to chemotherapy failure and multidrug resistance (MDR) in cancer cells. Representative secondary metabolites (SM) including phenolics (EGCG and thymol), terpenoids (menthol, aromadendrene, β-sitosterol-O-glucoside, and β-carotene), and alkaloids (glaucine, harmine, and sanguinarine) were evaluated as potential P-gp inhibitors (transporter activity and expression level) in P-gp expressing Caco-2 and CEM/ADR5000 cancer cell lines. Selected SM increased the accumulation of the rhodamine 123 (Rho123) and calcein-AM (CAM) in a dose dependent manner in Caco-2 cells, indicating that they act as competitive inhibitors of P-gp. Non-toxic concentrations of β-carotene (40 μM) and sanguinarine (1 μM) significantly inhibited Rho123 and CAM efflux in CEM/ADR5000 cells by 222.42% and 259.25% and by 244.02% and 290.16%, respectively relative to verapamil (100%). Combination of the saponin digitonin (5 μM), which also inhibits P-gp, with SM significantly enhanced the inhibition of P-gp activity. The results were correlated with the data obtained from a quantitative analysis of MDR1 expression. Both compounds significantly decreased mRNA levels of the MDR1 gene to 48% (p < 0.01) and 46% (p < 0.01) in Caco-2, and to 61% (p < 0.05) and 1% (p < 0.001) in CEM/ADR5000 cells, respectively as compared to the untreated control (100%). Combinations of digitonin with SM resulted in a significant down-regulation of MDR1. Our findings provide evidence that the selected SM interfere directly and/or indirectly with P-gp function. Combinations of different P-gp substrates, such as digitonin alone and together with the set of SM, can mediate MDR reversal in cancer cells.     

紫金龙的生物碱成分

紫金龙(Dactylicapnos scandens Hutch)是云南民间使用较普遍的草药,主要用于镇痛。前报报道了从紫金龙根中分离和鉴定了其中主要生物碱成分右旋异紫堇丁〔(+)isocorydine〕和普罗托品(protopine)。最近又从该植物根中分得两个生物碱成分,其量较少。经光谱分析鉴定为(+)紫堇丁〔(+)ccrydine〕(1)和(+)海罂粟碱〔(+)glaucine〕(2)。质谱测得二者的分子离子峰分别为m/z 341,355,并均为基峰,而且二者均出现M~+—43(M—CH_2NCH_3)的碎片离子峰,分别为m/z298,312。与异紫堇丁的红外光谱相似,生物碱紫堇丁的羟基由于同甲氧基成分子内氢     

Synergism of three-drug combinations of sanguinarine and other plant secondary metabolites with digitonin and doxorubicin in multi-drug resistant cancer cells

We determined the ability of some phytochemicals, including alkaloids (glaucine, harmine, and sanguinarine), phenolics (EGCG and thymol), and terpenoids (menthol, aromadendrene, β-sitosterol-O-glucoside, and β-carotene), alone or in combination with the saponin digitonin to reverse the relative multi-drug resistance of Caco-2 and CEM/ADR5000 cells to the chemotherapeutical agent doxorubicin. The IC₅₀ of doxorubicin in Caco-2 and CEM/ADR5000 was 4.22 and 44.08 μM, respectively. Combination of non-toxic concentrations of individual secondary metabolite with doxorubicin synergistically sensitized Caco-2 and CEM/ADR5000 cells, and significantly enhanced the cytotoxicity of doxorubicin. Furthermore, three-drug combinations (secondary metabolite + digitonin + doxorubicin) were even more powerful. The best synergist was the benzophenanthridine alkaloid sanguinarine. It reduced the IC₅₀ value of doxorubicin 17.58-fold in two-drug combinations (sanguinarine + doxorubicin) and even 35.17-fold in three-drug combinations (sanguinarine + digitonin + doxorubicin) in Caco-2 cells. Thus synergistic drug combinations offer the possibility to enhance doxorubicin efficacy in chemotherapy.     

Alkaloid chemotypes of Glaucium flavum (Papaveraceae) from Bulgaria

The alkaloid pattern of Glaucium flavum Crantz. from four natural populations in Bulgaria were investigated and six aporphine, two protopine and one morphinane alkaloids were determined. In accordance with the particular content and composition of alkaloids and the different localities of the species three alkaloid chemotypes were suggested. The first one contains aporphines and protopines with a main alkaloid glaucine. The second chemotype contains again aporphine and protopine alkaloids but the main alkaloid is isocorydine and the third chemotype contains besides these two types of alkaloids and the morphinane alkaloid salutaridine.     

Inhibition of nonenzymic lipid peroxidation by benzylisoquinoline alkaloids.

A group of benzylisoquinoline alkaloids, including five simple benzylisoquinolines, three phtalideisoquinolines, six aporphines, three protoberberines, and two benzophenanthridines, have been studied as inhibitors of lipid peroxidation stimulated by Fe2+/cysteine in rat liver microsomal fractions. Protopapaverine, apomorphine, laudanosoline, tetrahydroberberine, isoboldine, bulbocapnine, boldine, anonaine, glaucine, and stepholidine showed antiperoxidative effects, and structure-activity relationships were established. In simple benzylisoquinolines, the presence of phenolic hydroxyls or similar reactive groups is necessary for inhibition of peroxidation, while in aporphines and protoberberines nonhydroxylated compounds can exert antiperoxidative effects. The phtalideisoquinolines and benzophenanthridines tested were inactive.     

延胡索分类的化学证据

东阳产延胡索与大连产齿瓣延胡索经成分分离和TLC、HPLC对比,发现延胡索以啊扑啡类生物碱如glaucine为主,而齿瓣延胡索则含corynoline类生物碱。根据生物碱的类型及含量比较,二者有明显差异,结合延胡索的植物形态和植化分类特征判断,将延胡索作为与齿瓣延胡索近缘的独立种处理较为合理,即为Corydalis yanhusuo W. T. Wang ex Z.Y. Su et C. Y. Wu     

Preparative isolation of alkaloids from Dactylicapnos scandens using pH-zone-refining counter-current chromatography by changing the length of the separation column

pH-Zone-refining counter-current chromatography was successfully applied for the preparative separation of alkaloids from Dactylicapnos scandens. The two-phase solvent system was composed of petroleum ether-ethyl acetate-methanol-water (3:7:1:9, v/v), where 20 mM of triethylamine (TEA) was added to the upper phase as a retainer and 5 mM of hydrochloric acid (HCl) to the aqueous phase as an eluter. In this experiment, the apparatus with an adjustable length of the separation column was used for the separation of alkaloids from D. scandens and the resolution of the compounds can be remarkably improved by increasing the length of the separation column. As a result, 70 mg protopin, 30 mg (+) corydine, 120 mg (+) isocorydine and 40 mg (+) glaucine were obtained from 1.0 g of the crude extracts and each with 99.2%, 96.5%, 99.3%, 99.5% purity as determined by HPLC. The chemical structures of these compounds were confirmed by positive ESI-MS and (1)H NMR.     

Antioxidant Action of Benzylisoquinoline Alkaloids

The antioxidant action of a series of benzylisoquinoline alkaloids has been investigated. Laudanosoline, protopapaverine, anonaine, apomorphine, glaucine, boldine, bulbocapnine, tetrahydroberberine and stepholidine produced a dose-dependent inhibition of microsomal lipid peroxidation induced by Fe²⁺/ascorbate, CCl₄/NADPH or by Fe³⁺ADP/NADPH. Apomorphine exerted the highest inhibitory effects in the three systems of induction used, with a potency higher than propyl gallate. Laudanosoline was particularly effective in the first system, while bulbocapnine and anonaine were more potent when CCl₄/NADPH or Fe³⁺ -ADP/NADPH were used as inducers. Laudanosoline, protopapaverine, apomorphine, tetrahydroberberine and stepholidine were also potent inhibitors of nitroblue tetrazolium (NBT) reduction. The presence of a free hydroxyl group or preferably of a catechol group is a feature relevant for inhibition of lipid peroxidation and NBT reduction, nevertheless the antioxidant activity of benzylisoquinoline alkaloids cannot be only ascribed to the formation of phenoxy radicals and other free radical species may be formed during aporphine and tetrahydroprotoberberine oxidation. The influence of this series of compounds on the time course of lipid peroxidation suggests that some of them, like apomorphine and boldine act as chain-breaking antioxidants.     

A new species of Hemibrycon (Characiformes,Characidae) from the upper San Juan River drainage,Pacific versant,Colombia

Hemibrycon sanjuanensis, new species, is described from the upper San Juan River drainage, Pacific versant, Colombia. It is distinguished from Hemibrycon boquiae, Hemibrycon brevispini, Hemibrycon cairoense, Hemibrycon colombianus, Hemibrycon mikrostiktos, Hemibrycon metae, Hemibrycon palomae, Hemibrycon rafaelense and Hemibrycon tridens by the presence of a circular or oblong humeral spot that is located two scales posterior to the opercle (vs. 3–4 scales in Hemibrycon palomae, Hemibrycon rafaelense, Hemibrycon brevispini and Hemibrycon cairoense, and 0–1 scales, in Hemibrycon metae and Hemibrycon boquiae). It further differs from Hemibrycon colombianus in having a round or oblong humeral spot (vs. rectangular). It differs from Hemibrycon beni, Hemibrycon dariensis, Hemibrycon divisorensis, Hemibrycon helleri, Hemibrycon huambonicus, Hemibrycon inambari, Hemibrycon jabonero, Hemibrycon jelskii, Hemibrycon mikrostiktos, Hemibrycon polyodon, Hemibrycon quindos, Hemibrycon raqueliae, Hemibrycon santamartae, Hemibrycon surinamensis, Hemibrycon taeniurus, Hemibrycon tridens, and Hemibrycon yacopiae in having melanophores on the posterior margins of the scales along the sides of body (vs. lacking melanophores on margins of scales along entire length of the sides of body). The new species differs from all congeners mentioned above in having, among other features, six teeth in the outer premaxillary row arranged in a straight line (vs. five or fewer teeth not arranged in straight line except Hemibrycon cairoense with two to six teeth in the outer premaxillary row).     

Salt lakes of La Mancha (Central Spain): A hot spot for tiger beetle (Carabidae,Cicindelinae) species diversity

The tiger beetle assemblage of the wetlands of La Mancha (central Spain) comprises nine species: Calomera littoralis littoralis, Cephalota maura maura, Cephalota circumdata imperialis, Cephalota dulcinea, Cicindela campestris campestris, Cicindela maroccana, Cylindera paludosa, Lophyra flexuosa flexuosa, and Myriochila melancholica melancholica. This assemblage represents the largest concentration of tiger beetles in a single 1º latitude / longitude square in Europe. General patterns of spatial and temporal segregation among species are discussed based on observations of 1462 specimens registered during an observation period of one year, from April to August. The different species of Cicindelini appear to be distributed over space and time, with little overlapping among them. Three sets of species replace each other phenologically as the season goes on. Most of the species occupy drying or dried salt lakes and salt marshes, with sparse vegetation cover. Spatial segregation is marked in terms of substrate and vegetation use. Calomera littoralis and Myriochila melancholica have been observed mainly on wet soils; Cephalota circumdata on dry open saline flats; Cephalota dulcinea and Cylindera paludosa in granulated substrates with typical halophytic vegetation; Cephalota maura is often present in man-modified areas. Cephalota circumdata and Cephalota dulcinea are included as species of special interest in the list of protected species in Castilla–La Mancha. Conservation problems for the Cicindelini assemblage arise from agricultural activities and inadequate use of sport vehicles. Attempts at restoring the original habitat, supressing old semi-industrial structures, may affect the spatial heterogeneity of the lakes, and have an effect on Cicindelinae diversity.