Sialylation reactions with 5-N,7-O-carbonyl-protected sialyl donors: unusual stereoselectivity with nitrile solvent assistance.

A 5-N,7-O-carbonyl-protected sialyl donor was synthesized, and, unexpectedly, this donor showed beta-selectivity (alpha/beta = 1/2.4-1/20) on coupling with sugar acceptors in acetonitrile upon treatment with various promoter systems. For the coupling reaction in dichloromethane, a modified Ellervik's method (IBr and AgClO(4).H(2)O) was highly effective in activating the 5-N,7-O-carbonyl donor, providing moderate alpha-selectivity (alpha/beta = ~1.8/1).

N-trans-feruloyltyramine as a melanin biosynthesis inhibitor.

In this study, we examined the effect of N-trans-feruloyltyramine (FA) on melanogenesis in mouse B16 melanoma cells. Melanogenesis was inhibited by FA in a dose-dependent manner. FA exhibited a greater potency than kojic acid as a standard inhibitor of melanogenesis. Moreover, treatment of B16 melanoma cells with FA was found to cause marked decreases in the expression levels of tyrosinase. FA-induced downregulation of tyrosinase resulted in suppression of melanin biosynthesis in murine B16 melanoma cells.

Preparation of aromatic beta-selenolactams and their bioactivities as agricultural chemicals.

The purpose of this study was to investigate the possibility of aromatic beta-selenolactams being used in agricultural chemicals. A series of beta-selenolactams with aromatic substituents at the 1-, 2- and 3-positions were synthesized and their bioactivities were evaluated. Acarianicidal and insecticidal activity against common destructive insects, antibacterial activity against seven common plant pathogens, and plant growth activity of typical food crops were investigated. We found that introduction of 4-chloro and 4-methyl groups on 2- or 3-phenyl groups of the beta-selenolactam ring brought about acarianicidal activity against adults and eggs of Plutella xylostella. However, except for moderate to weak effect on fatality of Culex pipiens molestus Forskal, insecticidal activity against two other kinds of insects, antibacterial activity against plant pathogens, and activity on plant growth regulation were not detected among the beta-selenolactam derivatives.

Synthesis of novel selenapenams, selenacephems, and selenazepines using a 2-(trimethylsilyl)ethyl protection approach.

Selenapenams, selenacephems, and selenazepines were synthesized using a 2-(trimethylsilyl)ethyl (TSE) protection approach in an extremely simple way. TSE protection for selenium is used for the first time in the synthesis of selenium-containing beta-lactam. Novel intramolecular cycloaddition reaction of selenium with alkynes and allenes is used in the present synthesis.

Isoselenocyanates: a powerful tool for the synthesis of selenium-containing heterocycles.

Selenium-containing heterocyclic compounds have been well recognized, not only because of their remarkable reactivities and chemical properties, but also because of their diverse pharmaceutical applications. In this context, isoselenocyanates have been emerged as a powerful tool for the synthesis of selenium-containing heterocycles, since they are easy to prepare and store and are safe to handle. In this review the recent advances in the development of synthesis methods for selenium-containing heterocycles from isoselenocyanates are presented and discussed.

The isolation of secondary metabolites and in vitro potent anti-cancer activity of clerodermic acid from Enicosanthum membranifolium.

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.

The synthesis of 1-thia-6-oxa-6alambda(4)-seleno-3-azapentalene and a 3H-1,2,4-dithiazole.

The reaction of thiocarbamoyl isoselenocyanate with a carbanion gave 1-thia-6-oxa-6alambda(4)-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.

Bis-(2-amino-5-selenazoyl) ketone as a superoxide anion-scavenger.

We investigated the superoxide anion scavenging effects of 2-amino-1,3- selenazoles and bis-(2-amino-5-selenazoyl) ketones using a highly sensitive quantitative chemiluminescence method. At 166 microM, the 2-amino-1,3-selenazoles and bis-(2-amino-5-selenazoyl) ketones scavenged in the range of 10.0 to 80.0% of O(2)(-). Bis[2-dimethylamino-5-(1,3-selenazolyl)] ketone exhibited the strongest superoxide anion-scavenging activity among the six kinds of 2-amino-1,3-selenazoles and three kinds of bis-(2-amino-5-selenazoyl) ketones. The 50% inhibitory concentration (IC(50)) of bis[2-dimethylamino-5-(1,3-selenazolyl)] ketone was determined to be 37.1 microM. Thus, bis[2-dimethylamino-5-(1,3-selenazolyl)] ketone acted in vitro as effective and potentially useful O(2)(-) scavenger.

2-(4-Methylphenyl)-1,3-selenazol-4-one induces apoptosis by different mechanisms in SKOV3 and HL 60 cells.

We examined the ability of the synthetic selenium compound, 2-(4-methylphenyl)-1,3-selenazol-4-one (hereafter designated 3a), to induce apoptosis in a human ovarian cancer cell line (SKOV3) and a human leukemia cell line (HL-60). Flow cytometry showed that 3a treatment induced apoptosis in both cell lines to degrees comparable to that of the positive control, paclitaxel. Apoptosis was measured by PS externalization, DNA fragmentation and decreased mitochondrial membrane potential (MMP). However, analysis of the mechanism of action revealed differences between the responses of the two cell lines. Treatment with 3a arrested the cell cycle and induced caspase-3 activation in HL-60 cells, but not in SKOV3 cells. In contrast, 3a treatment induced apoptosis through translocation of AIF, a novel pro-apoptotic protein, in SKOV3 cells, but not in HL-60 cells. Collectively, our data demonstrated that 3a induced apoptosis in both cell lines, but via different action mechanisms.

Regulation of melanin synthesis by selenium-containing carbohydrates.

This study reports depigmenting potency of selenium-containing carbohydrates, which would be based upon the finding of direct inhibition to mushroom tyrosinase. Two selenoglycosiede, SG-3 (bis(2,3,4-tri-O-acetyl-beta-D-arabinopyranosyl) selenide) and SG-8 (4'-methylbenzoyl 2,3,4,6-tetra-O-acetyl-D-selenomanopyranoside) among eleven selenium-containing compounds examined, were discovered to be effective depigmenting compounds on a mushroom tyrosinase inhibitory assay. SG-3 exhibited a competitive inhibition effect that was similar to kojic acid, well-known tyrosinase inhibitor. At 100 microM and 150 microM, SG-8 had an uncompetitive inhibitory effect that was higher than kojic acid. A study of a melan-a cell originated-tyrosinase inhibition assay showed that SG-8 had a lower inhibitory effect than kojic acid. SG-3 showed a similar inhibition effect to kojic acid on the melan-a cell-originated tyrosinase inhibitory assay. SG-8 showed dose-dependently cytotoxicity in a study of inhibition melanin synthesis by melan-a cells. Most melan-a cells did not survive after being treated with 20 microM of SG-8. At 10 microM, SG-3 inhibited melanin synthesis in the melan-a cells, and the effect was similar to phenylthiourea, which is a well-known inhibitor of melanin synthesis. Therefore, SG-3 is a new candidate for depigmenting reagents.

Superoxide anion-scavenging effect of 2-amino-1,3-selenazoles.

We investigated the superoxide anion scavenging effects of thirteen 2-amino-1,3-selenazoles using a highly sensitive quantitative chemiluminescence method. At 166 microM, the 2-amino-1,3-selenazoles scavenged in the range of 14.3 to 96.7% of O2-. 2-Piperidino-1,3-selenazole and 4-phenyl-2-piperidino-1,3-selenazole exhibited the strongest superoxide anion-scavenging activity among the 2-amino-1,3-selenazoles. The 50% inhibitory concentrations (IC50) of 2-piperidino-1,3-selenazole and 4-phenyl-2-piperidino-1,3-selenazole were determined to be 4.03 microM and 92.6 microM, respectively. Thus, these compounds acted in vitro as effective O2- scavengers.

A facile method for beta-selenoglycoside synthesis using beta-p-methylbenzoyl selenoglycoside as the selenating unit.

[reaction: see text] The reaction between alpha-glycosyl bromides and potassium p-methylselenobenzoate yields beta-p-methylbenzoyl selenoglycosides. The acyl selenoglycosides were activated by the action of a secondary amine and Cs2CO3 to produce an anomeric selenolate anion, which reacted in situ with various electrophiles to yield novel selenoglycosides while retaining the anomeric stereochemistry.

Potent inhibitory effects of N-aryl S-alkylthiocarbamate derivatives on the dopa oxidase activity of mushroom tyrosinase.

This study reports the potent inhibitory effect of N-aryl S-alkylthiocarbamate derivatives on mushroom tyrosinase (MT) activity. N-Aryl S-alkylthiocarbamate derivatives were found to exhibit a potent inhibitory effect on the dopa (3,4-dihydroxyphenylalanine) oxidase activity of mushroom tyrosinase. Most of the N-aryl S-alkylthiocarbamate derivatives (compounds from A to J) exhibited higher inhibitory effects than kojic acid (IC50=318 microM), a well known tyrosinase inhibitor. Tyrosinase was the most inhibited by S-phenetyl N-phenylthiocarbamate (compound E, IC50=7.25 microM), and this inhibition was 44 times stronger than that of kojic acid. Compound E exhibited 95.0% of inhibition at 100 microM. A kinetic study of MT inhibition by compound E using the Lineweaver-Burk plots analysis was performed. And the kinetics profiles observed suggest that compound E competitively inhibits MT.

Inhibition of tyrosinase activity by N,N-unsubstituted selenourea derivatives.

This study investigated inhibitory effects of N,N-unsubstituted selenourea derivatives on tyrosinase activity. Three types of N,N-unsubstituted selenoureas derivatives exhibited inhibitory effect on dopa (3,4-dihydroxyphenylalanine) oxidase activity of mushroom tyrosinase. Compound D at a concentration of 200 microM exhibited 55.5% of inhibition on dopa oxidase activity of mushroom tyrosinase. This inhibitory effect was higher than that of kojic acid (39.4%), a well known tyrosinase inhibitor. Moreover, the compound D identified as a noncompetitive inhibitor by Lineweaver-Burk plot analysis. In addition, compound D also inhibited the melanin production in melan-a cells.

Selenocarbamates are effective superoxide anion scavengers in vitro.

We investigated the superoxide anion-scavenging effects of six selenocarbamates and four thiocarbamates, using a highly sensitive quantitative chemiluminescence method. At 333 nM, six selenocarbamates and four thiocarbamates scavenged in the range of 2.9-68.7% of O(2)*-. Se-methyl N-phenylselenocarbamate and Se-methyl N-(4-methylphenyl)selenocarbamate exhibited the strongest superoxide anion-scavenging activity among the Se-selenocarbamates. In contrast, the corresponding S-thiocarbamates had moderate inhibitory effect. The 50% inhibitory concentrations (IC(50)) of Se-methyl-N-phenylselenocarbamate and Se-methyl-N-(4-methylphenyl)selenocarbamate were determined to be 140 nM and 162 nM, respectively. Thus, these compounds acted in vitro as effective and potentially useful O(2)*- scavengers.

Selenoureas and thioureas are effective superoxide radical scavengers in vitro.

Oxygen radicals, such as superoxide radicals, embellishing DNA, protein, lipids, etc., and carrying out the obstacle of the function of a cell is known. It depends for the oxidant level in the living body on the balance of a generation system and an elimination system of oxygen radicals, and research which controls an oxidant level in the living body is briskly done by taking in the substance which eliminates an oxygen radical. We investigated scavenging effects of superoxide radicals by selenoureas and thioureas using a highly sensitive and quantitative chemiluminescence method. At 330 nM, five selenoureas and five thioureas scavenged fractions of superoxide radicals (O2-) ranging from 8.4% to 87.6%. Among five N,N-unsubstituted selenoureas and N,N-unsubstituted thioureas 1-selenocarbamoylpiperidine and 1-thiocarbamoylpyrrolidine were the most effective scavengers. A possibility that selenoureas could use it as a new superoxide anion-scavenging substance from the result of this research became clear.

Synthesis of 3-acyl-1-alkyl-2-alkylseleno-1-cyclobutene using alkyneselenolate.

The reaction of lithium alkyneselenolate with alpha,beta-unsaturated ketone and then alkyl or acyl halide afforded 3-acyl-1-alkyl-2-alkylseleno-1-cyclobutene. The structure of the cyclobutene was elucidated by IR, MS, (1)H, (13)C, and (77)Se NMR, COSY, HMQC, and HMBC data and X-ray analysis.

Tertiary selenoamide compounds are useful superoxide radical scavengers in vitro.

We investigated the scavenging effects of tertiary selenoamide compounds for super oxide radicals using a highly sensitive and quantitative chemiluminescence method. At 333 nM, tertiary selenoamide compounds scavenged 25.8-81.6% of O(2)(-). N-(Phenylselenocarbonyl) piperidine was the most effective scavenger of superoxide radicals. While N,N-diethyl-2-selenonaphthylamide and N,N-diethyl-4-chloroselenobenzamide was a moderately effective scavenger of superoxide radicals. The IC(50) of N-(phenylselenocarbonyl) piperidine and N,N-diethyl-2-selenonaphthylamide were determined to be 110 and 182 nM, respectively. The results suggest that tertiary selenoamide compounds are useful scavengers of superoxide radicals.

1,3-selenazol-4-one derivatives inhibit inducible nitric oxide-mediated nitric oxide production in lipopolysaccharide-induced BV-2 cells.

Activated microglia extensively produce nitric oxide (NO) by inducing expression of inducible NO synthase (iNOS). NO plays a deleterious role in brain inflammation and neuronal death. In the present study, we investigated the effects of 1,3-selenazol-4-one derivatives (Sz-A, B, C, D and E) on NO production and iNOS expression in lipopolysaccharide (LPS)-induced BV-2 cells, a murine microglia cell line. Among these compounds, Sz-B and C remarkably inhibited LPS-induced NO production relative to that of Sz-A, D, and E at 5 microM in BV-2 cells. Sz-B and C dose-dependently inhibited NO production at 1, 5, and 10 microM without toxicity to BV-2 cells. Sz-B and C also dose-dependently suppressed iNOS expression at the same concentrations in LPS-induced BV-2 cells. This result suggests that Sz-B and C inhibit iNOS-mediated NO production in LPS-induced BV-2 cells. Structurally, Sz-B and C bear an ethyl or methyl group at the 5 positions of the 4-selenazolone skeletons, which could play an important role in inhibiting iNOS-mediated NO production.

Inhibitory effects of 1,3-selenazol-4-one derivatives on mushroom tyrosinase.

This study reports depigmenting potency of 1,3-selenazol-4-one derivatives, which would be based upon the finding of direct inhibition to mushroom tyrosinase. 1,3-Selenazol-4-one derivatives exhibited inhibitory effect on dopa oxidase activity of mushroom tyrosinase. In this study, inhibitory effects of six kinds of 1,3-selenazol-4-one derivatives (A, B, C, D, E and F) on mushroom tyrosinase were investigated. Compounds at a concentration of 500 microM exhibited 33.4-62.1% of inhibition on dopa oxidase activity of mushroom tyrosinase. Their inhibitory effects were higher than that of kojic acid (31.7%), a well known tyrosinase inhibitor. 2-(4-Methylphenyl)-1,3-selenazol-4-one (A) exhibited the strongest inhibitory effect among them dose-dependently and in competitive inhibition manner.