Cinnamomum parthenoxylon tree belongs to the Lauraceae family. In this study, flavonoid rutinosides were isolated from C. parthenoxylon leaves and their hepatoprotective and antioxidant activity were evaluated. The EtOAc fraction of C. parthenoxylon leaves showed potent hepatoprotective activity on tert-butyl hydroperoxide-induced cytotoxicity in HepG2 cells and also higher antioxidant activity. Ultra-performance liquid chromatography electrospray ionization mass spectrometry analysis revealed that flavonoid rutinosides; rutin, nicotiflorin, and isorhoifolin are major constituents in the EtOAc fraction. The catechol group on B ring in the structure of rutin holds potential for hepatoprotective and antioxidant activity.

•Se-containing organic scaffolds synthesis.•Se-containing heterocycles synthesis.•Se-containing bioactive organic scaffolds synthesis.•Synthesis of ebselen or ethaselen and related molecules.Recent, many methods have been reported for the synthesis of selenium-containing bioactive scaffolds because of their interesting reactivity and potential pharmaceutical applications. This review describes developments in the synthesis of selenium-containing biologically relevant scaffolds reported during the last decade.Download high-res image (150KB)Download full-size image

Xylosides are small molecules that serve as primers of glycosaminoglycan biosynthesis. Xyloside mediated modulation of biological functions depends on the extent of priming activity and fine structures of primed GAG chains. In earlier studies, copper (Cu) catalyzed synthesis of click-xylosides and their priming activity were extensively documented. In the current study, ruthenium (Ru) mediated catalysis was employed to synthesize xylosides with a 1,5-linkage between the xylose and the triazole ring instead of a 1,4-linkage as found in Cu-catalyzed click-xyloside synthesis. Mono- and bis-click-xylosides were synthesized using each catalytic method and their glycosaminoglycan priming activity was assessed in vitro using a cellular system. Ru-catalyzed click-xylosides showed a higher priming activity as measured by incorporation of radioactive sulfate into primed glycosaminoglycan chains. This study demonstrates that altering the linkage of the aglycone to the triazole ring changes the priming activity. Computational modeling provides a molecular rationale for higher priming ability of Ru-mediated click-xylosides. Higher GAG priming activity is attributed to the formation of more stable interactions between the 1,5-linked xylosides and β-1,4-galactosyltransferase 7 (β4GalT7).Download high-res image (120KB)Download full-size image

Selenium-containing amino acids play a pivotal role as biomaterials for the synthesis of Se-dependent enzymes and repair proteins. Especially, selenocysteine and selenoglutathione are prominently involved in fundamental biological processes. In this study, a series of selenocysteine (Sec) and selenoglutathione (GSeH) derivatives were synthesized via 2-(trimethylsilyl)ethylselenation as a key step. Our findings suggested the relevance and application of a 2-(trimethylsilyl)ethylselenyl group to the Se-containing amino acid synthesis.Download high-res image (117KB)Download full-size image

Quercetin derivatives are widespread in the plant kingdom and exhibit various biological actions. The aim of this study was to investigate the structure–activity relationships of quercetin derivatives, with a focus on the influence of functional groups and sugar composition on their antioxidant capacity. A series of quercetin derivatives were therefore prepared and assessed for their DPPH radical scavenging properties. Isoquercetin O-gallates were more potent radical scavengers than quercetin. The systematic analysis highlights the importance of the distribution of hydroxy substituents in isoquercetin O-gallates to their potency.

In this study, we evaluated the in vitro cytotoxicity of fractions and isolated constituents from Cinnamomum parthenoxylon woods against human leukemia HL-60 and U937 cells. The n-Hex, EtOAc, and MeOH–H2O fractions of the woods inhibited cell proliferation in both cell lines. Our phytochemical investigation of the n-Hex and EtOAc fractions led to the isolation of lignans and phenylpropanoids, whose chemical structures were confirmed by spectroscopic analyses. All isolated compounds were evaluated for their in vitro antileukemic activity; especially, hinokinin and cubebin exhibited strong inhibition toward U937 cell proliferation. Morphological observation indicated that these cytotoxic actions were mediated by apoptosis. Our findings suggested that an oxygenated functional group at the C-9 position in dibenzylfuran skeleton contributed their potency. In addition, these results enhanced the ethnopharmacological value of C. parthenoxylon.

Coreopsis lanceolata is a perennial plant belonging to the Asteraceae family. In this study, flavonoid profile and antileukemic potential of yellow flowers of the plant were investigated. The total flavonoid content in EtOAc fraction of the flower methanol extract was found to be 420 mg/g and showed the inhibition of cell proliferation and possible induction of apoptosis in human leukemia HL-60 cells. Our phytochemical research led to the isolation of rare flavonoids including a flavanone, chalcones, and aurones; in particular, 4-methoxylanceoletin demonstrated the potent antiproliferative activity. Comparison with other Asteraceaeous flowers by UPLC–MS analysis indicated that the isolates are characteristic constituents of C. lanceolata.

In this paper, we report that a versatile method for the synthesis of 5′-selenium modified nucleosides has been explored on the basis of a 2-(trimethylsilyl)ethyl (TSE) selenyl group as a selenating donor. We demonstrate the broad utility of this method through direct introduction of various functional groups into 5′-TSE-selenonucleosides. This original method offers additional advantages for the preparation of these compounds, such as high functional group tolerance, ready availability of various electrophilic reagents, mild conditions, simple operation, and good yields. The utility of this approach is further demonstrated by the synthesis of Se-adenosyl-L-selenomethionine (SeAM) as a chemical reporter for methyltransferases.

Toona sinensis is a traditional Chinese medicine belonging to the Meliaceae family. The aim of this study was to identify the potential compounds responsible for anticancer activity of T. sinensis. The EtOAc extracts of leaves and woods of T. sinensis inhibited cell proliferation and induced apoptosis in human leukemia HL-60 cells. Our phytochemical research of these extracts led to the isolation of various polyphenolic constituents. The chemical structures were determined by spectroscopic analyses. Among isolates, gallic acid and loropetalin D showed inhibition of cell proliferation and possible induction of apoptosis in these cells. Overall, our results revealed the importance of T. sinensis as a chemopreventive medicinal plant. In addition, an analysis of structure–activity relationship indicated that the number of galloyl groups affects their antileukemic potency.

The Staudinger ketene–imine [2 + 2] cycloaddition reaction for conversion of α-heteroatom-substituted exocyclic imines to C4 heterocyclic spiro-β-lactams has rarely been investigated due to their instability. Herein, we describe the Staudinger reaction between ketenes and α-selenium-substituted exocyclic imines to synthesize C4 spiro-β-lactams.

Utilizing aldehyde-substituted vinylogous carbonates and 1,3-diketones, a simple protocol is presented for the synthesis of 2,8-dioxabicyclo[3.3.1]nonane derivatives via Knoevenagel condensation followed by a hetero-Diels–Alder reaction under green reaction conditions. The structure of a key product is unequivocally confirmed by X-ray crystallography.

Flavonoids are widely occurring polyphenols that are found in plants. The aim of this study was to investigate the structure–activity relationships of 5,7-dihydroxyflavones, with a focus on the effect of B ring structure substitution on the antiproliferative effects of the compounds in human leukemia HL-60 cells. We prepared a series of 5,7-dihydroxyflavones and evaluated their ability to inhibit the proliferation of HL-60 cells by using the MTT assay. The apoptosis- and cell differentiation-inducing ability of the most potent flavones were investigated using staining and morphological analyses. This study explored the antileukemic and chemopreventive potency of 5,7-dihydroxyflavones, particularly diosmetin and chrysoeriol, which have both hydroxy and methoxy groups on the B ring.

A new ring A-seco triterpenoid, sentulic acid, along with a known oleanane-type triterpenoid, 3-oxoolean-12-en-27-oic acid, were isolated from the Indonesian plant Sandoricum koetjape Merr. Their chemical structures were elucidated by spectroscopic analysis. In addition, the cytotoxic effects of these compounds on human promyelocytic leukemia HL-60 cells were studied. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and trypan blue dye exclusion tests showed that sentulic acid and 3-oxoolean-12-en-27-oic acid were able to induce cytotoxicity in these cells. Furthermore, morphological examination and DNA fragmentation analysis indicated that these cytotoxic effects were mediated by apoptosis.

Selenium represents an essential element for organisms as various diseases can result from selenium deficiency. As a consequence, selenium-containing heterocycles are of considerable biochemical and pharmacological relevance. Selenium-containing heterocycles are often less stable than the corresponding sulfur analogues. Therefore, the investigation of new methods for the synthesis of small selenium-containing building blocks is of considerable interest. This review describes the use of biologically significant selenium-containing heterocycles from the viewpoint of chemical structures.Highlights► Selenium represents an essential element for organisms. ► As selenium containing is very important for the organism, various diseases can result from selenium deficiency. ► As a consequence, selenium containing heterocycles are of considerable biochemical and pharmacological relevance. ► Therefore, the investigation of new methods for the synthesis of small selenium-containing building blocks is of considerable interest. ► This review describes the use of biological significant selenium-containing heterocycles from the viewpoint of chemical structures.

Tricin (4′,5,7-trihydroxy-3′,5′-dimethoxyflavone) has demonstrated diverse biological activities. This compound has a high anti-human cytomegalovirus (HCMV) activity; however, its oral availability is low. To improve its bioavailability, we synthesized tricin−amino acid derivatives as prodrugs and investigated their cell permeability, stability in vitro, and oral availability in vivo. The results demonstrated that the tricin−alanine−glutamic acid conjugate exhibited enhanced permeability, stability in MDCK cells, and excellent bioavailability after oral administration in Crl:CD (SD) male rats. Tricin−alanine−glutamic acid conjugate is a potential new anti-HCMV drug.

The bis-2-(trimethylsilyl)ethyl diselenide was prepared and used as a selenating reagent for the insertion of the 2-(trimethylsilyl)ethylseleno group at the C-4 position of the azetidinones. Bis-4-(azetidin-2-one) diselenides were used for the first time as a key intermediate for the synthesis of selenium-containing β-lactams i.e. selenacephams and selenacephems.

Reaction of isoselenocyanates with aminoacetonitriles afforded 4-amino-2-selenoxo-1,3-imidazole-2-selenones, whereas reaction with aminopropionitriles led to selenoureas. We confirmed that it is easy to distinguish between selenoamides and selenoureas by comparison of their chemical shift differences in the 77Se NMR spectra.

We synthesized 23 6-alkoxycoumarin derivatives, 20 of which are novel compounds. The structures of all compounds were confirmed by NMR, MS, and elemental analysis, and their antifeedant and termiticidal activities against Coptotermes formosanus Shiraki were examined. In a no-choice test, 6-(2-pentynyloxy)coumarin (2v), 6-(2-butynyloxy)coumarin (2u), 6-(2-octynyloxy)coumarin (2w), and 6-methoxycoumarin (2a), demonstrated high termiticidal activity at a concentration of 10 μmol. At a concentration of 5 μmol, 6-(2-butynyloxy)coumarin (2u) produced the highest mortality among the compounds tested. On the other hand, all of the 6-alkoxycoumarins showed antifeedant activity at both concentrations, except 6-octadecyloxycoumarin (2j) that was inactive at 5 μmol. Among the 23 compounds and the control, 6-ethoxycoumarin (2b), 6-isopropoxycoumarin (2d), and 6-isobutoxycoumarin (2f) exhibited the highest antifeedant activity with no mass loss (0.00%) at a concentration of 10 μmol. Our findings indicate that the presence of alkenyloxy and alkynyloxy groups was important for the termiticidal activity, while the incorporation of alkoxy groups with longer alkyl chains tended to reduce both the termiticidal and antifeedant activities. Furthermore, short chain alkoxy and arylalkoxy-substituted analogs showed good antifeedant activity, but methoxy groups on the benzene ring had a negative effect.

We isolated eight phenolic constituents from Fragaria ananassa Duch. (strawberry) and determined their structures using 1D, 2D-NMR. Among the isolated compounds, linocinnamarin (LN), 1-O-trans-cinnamoyl-β-d-glucopyranose (CG), and cinnamic acid (CA) exhibited antigen (Ag)-stimulated degranulation in rat basophilic leukemia RBL-2H3 cells. In order to reveal the underlying mechanisms, we examined the effects of LN and CA on cellular responses induced by antigen stimulation. Treatment with both LN and CA markedly inhibited antigen-stimulated elevation of intracellular free Ca2+ concentration and reactive oxygen species (ROS). Both LN and CA suppressed Ag-stimulated spleen tyrosine kinase (Syk) activation. These results indicate that inhibition of antigen-stimulated degranulation by LN and CA is mainly due to inactivation of Syk/phospholipase Cγ (PLCγ) pathways. Our findings suggest that LN and CA isolated from F. ananassa Duch. (strawberry) could be beneficial agents for alleviating symptoms of type I allergy.

We isolated three chalcone glycosides along with other glycoside constituents from the aerial parts of Brassica rapa L. ‘hidabeni’ and examined the effects of these compounds on the antigen-stimulated degranulation in rat basophilic leukemia RBL-2H3 cells. Treatments with both 4′-O-β-d-glucopyranosyl-4-hydroxy-3′-methoxychalcone (C1) and 4′-O-β-d-glucopyranosyl-3′,4-dimethoxychalcone (C2) markedly inhibited antigen (Ag)-stimulated degranulation. To gain further insight into the inhibitory mechanisms by C1 and C2, we examined early intracellular signaling events, Ca2+ mobilization and intracellular reactive oxygen species (ROS) production. Both C1 and C2 did not affect early intracellular signaling events but exhibited the suppression of intracellular ROS production through NADPH oxidase (NOX) inactivation. From these results, we proposed that the inhibitory effects of C1 and C2 on Ag-stimulated degranulation were mainly due to suppression of intracellular Ca2+ elevation by suppression of intracellular ROS production through NOX inactivation. Our findings suggest that C1 and C2 would be beneficial to alleviate symptoms of type I allergy.

A morroniside cinnamic acid conjugate was prepared and evaluated on E-selectin mediated cell–cell adhesion as an important role in inflammatory processes. 7-O-Cinnamoylmorroniside exhibited excellent anti-inflammatory activity (IC50 = 49.3 μM) by inhibiting the expression of E-selectin; further, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC50 = 88.2 μM), 7-O-methylmorroniside, and morroniside itself. As a result, 7-O-cinnamoylmorroniside was observed to be a potent inhibitor of TNF-α-induced E-selectin expression.

A phytochemical investigation of the aerial parts of Brassica rapa L. ‘hidabeni’, turnip resulted in the isolation of three new chalcone glycosides, 4′-O-β-d-glucopyranosyl-4-hydroxy-3′-methoxychalcone (1), 4′-O-β-d-glucopyranosyl-3′,4-dimethoxychalcone (2) and 4,4′-di-O-β-d-glucopyranosyl-3′-methoxychalcone (3) along with three known glycosides. The structures of the three newly isolated chalcone glycosides were elucidated on the basis of 1D and 2D NMR and mass spectroscopy.

The antitermite (termiticidal and antifeedant) activity of Protium javanicum Burm. f. extract was investigated. The ethyl acetate fraction was active. Scopoletin (1), quercetin, and stigmasterol were isolated by bioassay-guided fractionation. Scopoletin had the highest activity among the three compounds. In order to investigate the structure-activity relationship (SAR) of the methoxy and hydroxy groups at the C-6 and C-7 positions of the coumarin skeleton, we synthesized several coumarin derivatives whose chemical structures are similar to scopoletin. Scopoletin exhibited the strongest termiticidal activity among the 10 compounds tested, followed by 6-methoxycoumarin (3), 6-hydroxycoumarin (7), and umbelliferone (8). All compounds except coumarin (9) showed antifeedant activity.

The stereoselective insertion of allyl-seleno moieties at the C(4) position of azetidinones and further ring-closing metathesis afforded novel selenium-containing bicyclic β-lactams.

The reaction of thiocarbamoyl isoselenocyanate with a carbanion gave 1-thia-6-oxa-6aλ4-seleno-3-azapentalene, which has a hypervalent selenium, as the major product. The by-products 3-diacylmethylidene-5-dimethylamino-3H-1,2,4-dithiazole and thiocarbamate thioanhydride were also formed.

Four compounds were isolated from Enicosanthum membranifolium. The structures of the compounds were confirmed by spectroscopic data. Their structures were determined as N-trans-feruloyltyramine, R-(−)-mellein, clerodermic acid, and salicifoline chloride as a quaternary alkaloid compound. The structures of R-(−)-mellein and salicifoline chloride were confirmed by using X-ray diffraction. Clerodermic acid was shown to induce potent apoptosis against human leukemia HL60 cells.

Twenty-three 7-alkoxycoumarins and related analogs were synthesized from 7-hydroxycoumarin by treatment with various alkyl/aryl/acyl halides and potassium carbonate in DMF. Their antifeedant and termiticidal activities against Coptotermes formosanus Shiraki were examined. Among the 23 compounds and control, 7-cyclohexyloxycoumarin (2k), exhibited the highest termiticidal activity in no-choice test, followed by 7-(4-nitrophenoxy)coumarin (2q), and 7-(2-butynyloxy)coumarin (2u) at 5 μmol/disc. On the other hand, all of 7-alkoxycoumarins showed antifeedant activity except 7-hexadecyloxycoumarin (2i) and 7-octadecyloxycoumarin (2j), while 7-ethoxycoumarin (2b) demonstrated the highest antifeedant activity. The results suggested that a presence of cyclohexyloxy and aryloxy groups at C-7 position of coumarin skeleton was found to be important for the termiticidal and antifeedant activities. Arylalkoxy groups having methoxy groups at benzene ring, alkenoxy, and alkynoxy groups led to analogs with good termiticidal activity, while the incorporation of alkoxy groups with longer alkyl chains tended to reduce both the termiticidal and antifeedant activities.Highlights► 23 kinds of 7-alkoxycoumarins were synthesized. ► 7-Cyclohexyloxycoumarin exhibited the highest termiticidal activity. ► 7-Ethoxycoumarin demonstrated the highest antifeedant activity. ► Cyclohexyloxy and aryloxy groups at C-7 of coumarin skeleton was important.

An active substance with high hyaluronidase inhibitory effect was isolated from the edible cyanobacterium Nostochopsis lobatus MAC0804NAN strain and characterized. The active component in the hot water extract was purified by anion exchange and gel filtration chromatography and was found to be a polysaccharide. The IC50 against hyaluronidase of the purified polysaccharide was 7.18 μg/ml whose inhibitory activity is 14.5 times stronger than that of disodium cromoglycate (DSCG), an anti-allergy medication. The carbohydrate composition which was analyzed by GC–MS and NMR was found to be composed mainly of glucose, glucuronic acid, fucose, 2-O-methylfucose, mannose, galactose and xylose.

•The termiticidal activity of n-hexane and methanol fractions of Acorus calamus Linn rhizomes against Coptotermes curvignathus Holmgren was investigated.•Both fractions have demonstrated strong termiticidal activity.•The activity of n-hexane fraction was stronger than that of the methanol fraction.•Based on GC-MS data, β-asarone was found to be a major constituent of n-hexane fraction (70.1%).•The β-asarone and α-asarone revealed strong termiticidal activity against C. curvignathus.The termiticidal activity of n-hexane and methanol fractions of Acorus calamus Linn rhizomes against Coptotermes curvignathus Holmgren was investigated. Both fractions have demonstrated strong termiticidal activity. The activity of n-hexane fraction was stronger than that of the methanol fraction. Based on GC-MS data, β-asarone was found to be a major constituent of n-hexane fraction (70.1%) and isolation of β-asarone was carried out on column chromatography to afford as a yellow oil in 59.1% yield. Furthermore, the antitermite properties of β-asarone and α-asarone of the isomer were investigated. Our data suggested that the two asarone isomers have insect control potential. These findings lead to the discovery of more environmentally friendly termiticides against C. curvignathus.Download full-size image

The reaction of thiocarbamoyl isoselenocyanate with a carbanion gave 1-thia-6-oxa-6aλ4-seleno-3-azapentalene, which has a hypervalent selenium, as the major product. The by-products 3-diacylmethylidene-5-dimethylamino-3H-1,2,4-dithiazole and thiocarbamate thioanhydride were also formed.

The stereoselective insertion of allyl-seleno moieties at the C(4) position of azetidinones and further ring-closing metathesis afforded novel selenium-containing bicyclic β-lactams.

In this paper, we report that a versatile method for the synthesis of 5′-selenium modified nucleosides has been explored on the basis of a 2-(trimethylsilyl)ethyl (TSE) selenyl group as a selenating donor. We demonstrate the broad utility of this method through direct introduction of various functional groups into 5′-TSE-selenonucleosides. This original method offers additional advantages for the preparation of these compounds, such as high functional group tolerance, ready availability of various electrophilic reagents, mild conditions, simple operation, and good yields. The utility of this approach is further demonstrated by the synthesis of Se-adenosyl-L-selenomethionine (SeAM) as a chemical reporter for methyltransferases.

The Staudinger ketene–imine [2 + 2] cycloaddition reaction for conversion of α-heteroatom-substituted exocyclic imines to C4 heterocyclic spiro-β-lactams has rarely been investigated due to their instability. Herein, we describe the Staudinger reaction between ketenes and α-selenium-substituted exocyclic imines to synthesize C4 spiro-β-lactams.