掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s11627-021-10189-x

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その他リンク： https://link.springer.com/article/10.1007/s11627-021-10189-x/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing Ltd  

Drug design using boron-containing heterocycles has attracted a great deal of attention because these compounds are believed to possess high biological activity. However, information on the synthetic methodology and pharmacokinetic profiling of boron-containing compounds is limited. In this study, we provide a new synthetic route for preparation of spiro-fused benzoxaborin derivatives and investigate their in vitro pharmacokinetic properties. Our efforts led to the successful construction of a chemical library of spiro-fused benzoxaborin derivatives with appropriate physicochemical and in vitro pharmacokinetic properties for oral drugs. These results indicate that the synthesized boron-containing compounds are therefore eligible for classification in a novel chemical library.

DOI： 10.1111/cbdd.13496

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Kyoji Ishida, Masahiro Shimizu, Yusuke Yamai, Itaru Natsutani, Shinichi Uesato, Yasuo Nagaoka, Takaaki Sumiyoshi,

DOI： 10.3987/COM-18-S(F)87

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Dysfunction of mitochondrial activity is often associated with the onset and progress of neurodegenerative diseases. Membrane depolarization induced by Na+ influx increases intracellular Ca2+ levels in neurons, which upregulates mitochondrial activity. However, overlimit of Na+ influx and its prolonged retention ultimately cause excitotoxicity leading to neuronal cell death. To return the membrane potential to the normal level, Na+/K+-ATPase exchanges intracellular Na+ with extracellular K+ by consuming a large amount of ATP. This is a reason why mitochondria are important for maintaining neurons. In addition, astrocytes are thought to be important for supporting neighboring neurons by acting as energy providers and eliminators of excessive neurotransmitters. In this study, we examined the meaning of changes in the mitochondrial oxygen consumption rate (OCR) in primary mouse neuronal populations. By varying the medium constituents and using channel modulators, we found that pyruvate rather than lactate supported OCR levels and conferred on neurons resistance to glutamate-mediated excitotoxicity. Under a pyruvate-restricted condition, our OCR monitoring could detect excitotoxicity induced by glutamate at only 10 mu M. The OCR monitoring also revealed the contribution of the N-methyl-D-aspartate receptor and Na+/K+-ATPase to the toxicity, which allowed evaluating spontaneous excitation. In addition, the OCR monitoring showed that astrocytes preferentially used glutamate, not glutamine, for a substrate of the tricarboxylic acid cycle. This mechanism may be coupled with astrocyte-dependent protection of neurons from glutamate-mediated excitotoxicity. These results suggest that OCR monitoring would provide a new powerful tool to analyze the mechanisms underlying neurotoxicity and protection against it.

DOI： 10.1002/syn.22067

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DOI： 10.3987/COM-18-S(T)82

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3987/COM-17-S(T)2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000475471

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Pigmentation in mammals is important for protection of skin and eyes from ultraviolet radiation. Dysregulation of pigmentation is often associated with other conditions that are not directly linked to pigmentation. Here, we isolated spontaneously occurring hypopigmented mice that occasionally experienced severe diarrhea during lactation. Treatment of these mice with dextran sulfate sodium salt, a conventional method to induce acute colitis, caused chronic diarrhea with granulomatous colitis. Gene mapping and sequencing revealed that the mice had a nonsense mutation in the Hermansky-Pudlak syndrome (Hps) 5 gene. As some HPS patients can develop granulomatous colitis, the simple induction of chronic colitis in spontaneously mutated Hps5-deficient mice may become an invaluable model for exploring treatment options in patients with HPS as well as other patients with inflammatory bowel disease.

DOI： 10.1111/pcmr.12504

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pigmentation in mammals is important for protection of skin and eyes from ultraviolet radiation. Dysregulation of pigmentation is often associated with other conditions that are not directly linked to pigmentation. Here, we isolated spontaneously occurring hypopigmented mice that occasionally experienced severe diarrhea during lactation. Treatment of these mice with dextran sulfate sodium salt, a conventional method to induce acute colitis, caused chronic diarrhea with granulomatous colitis. Gene mapping and sequencing revealed that the mice had a nonsense mutation in the Hermansky-Pudlak syndrome (Hps)5 gene. As some HPS patients can develop granulomatous colitis, the simple induction of chronic colitis in spontaneously mutated Hps5-deficient mice may become an invaluable model for exploring treatment options in patients with HPS as well as other patients with inflammatory bowel disease.

DOI： 10.1111/pcmr.12504

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cosmetic industries focus on developing materials and resources that regulate skin pigmentation. Melanin, the major pigment in human skin, protects the skin against damage from ultraviolet light. An ethanolic extract of the leaves of Callicarpa longissima inhibits melanin production in B16F10 mouse melanoma cells by suppressing microphthalmia-associated transcription factor (MITF) gene expression. Following purification and analysis using liquid chromatography-mass spectrometry (LC-MS), NMR, and biochemical assays, carnosol was determined to be responsible for the major inhibitory effect of the C. longissima extract on melanin production. Carnosol is an oxidative product of carnosic acid, whose presence in the extract was also confirmed by an authentic reference. The carnosol and carnosic acid content in the extract was approximately 16% (w/w). These results suggest that C. longissima is a novel, useful, and attractive source of skin-whitening agents.

DOI： 10.1007/s11418-015-0933-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

Cosmetic industries focus on developing materials and resources that regulate skin pigmentation. Melanin, the major pigment in human skin, protects the skin against damage from ultraviolet light. An ethanolic extract of the leaves of Callicarpa longissima inhibits melanin production in B16F10 mouse melanoma cells by suppressing microphthalmia-associated transcription factor (MITF) gene expression. Following purification and analysis using liquid chromatography-mass spectrometry (LC-MS), NMR, and biochemical assays, carnosol was determined to be responsible for the major inhibitory effect of the C. longissima extract on melanin production. Carnosol is an oxidative product of carnosic acid, whose presence in the extract was also confirmed by an authentic reference. The carnosol and carnosic acid content in the extract was approximately 16 % (w/w). These results suggest that C. longissima is a novel, useful, and attractive source of skin-whitening agents.

DOI： 10.1007/s11418-015-0933-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

The carbamate fungicide benomyl reportedly inhibited the growth of the human breast cancer cell line MCF-7 by inducing apoptosis. However, influence of benomyl on the expression and activity of aromatase of MCF-7 cells remains to be examined, since benomyl was identified as an endocrine disruptor. We here confirmed through cell cycle analysis and immunofluorescence staining that benomyl damaged microtubules and caused apoptosis. We also found that benomyl inhibited histone deacetylase (HDAC) 1 and accumulated acetylated histone H3 in MCF-7 cells. Additionally, benomyl enhanced the levels of aromatase protein and mRNA, albeit at high concentrations. It is thus likely that benomyl enhanced the promoter activity of the aromatase gene via acetylation of histone H3 as does the HDAC inhibitor Vorinostat. In conclusion, benomyl remains to be a risk factor as an endocrine disruptor for breast cancer. (C) 2014 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.etap.2014.11.032

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Memantine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, and is an approved drug for the treatment of moderate-to-severe Alzheimer's disease. We identified a mouse strain with a naturally occurring mutation and an ataxic phenotype that presents with severe leg cramps. To investigate the phenotypes of these mutant mice, we screened several phenotype-modulating drugs and found that memantine (10 mg/kg) disrupted the sense of balance in the mutants. Moreover, the mutant mice showed an attenuated optokinetic response (OKR) and impaired OKR learning, which was also observed in wild-type mice treated with memantine. Microsatellite analyses indicated that the Grid2 gene-deletion is responsible for these phenotypes. Patch-clamp analysis showed a relatively small change in NMDA-dependent current in cultured granule cells from Grid2 gene-deleted mice, suggesting that GRID2 is important for correct NMDA receptor function. In general, NMDA receptors are activated after the activation of non-NMDA receptors, such as AMPA receptors, and AMPA receptor dysregulation also occurs in Grid2 mutant mice. Indeed, the AMPA treatment enhanced memantine susceptibility in wild-

DOI： 10.3390/genes5041095

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：GEORG THIEME VERLAG KG  

Non-small-cell lung carcinomas do not sufficiently respond to cancer chemotherapeutic drugs. Combination effects of cancer chemotherapy drugs (paclitaxel and carboplatin) with nobiletin or powdered Shiikuwasha extract from Citrus depressa were examined by isobologram and combination index analyses. It was demonstrated that the combination generated a synergistic inhibitory effect against the proliferation of the human non-small-cell lung carcinoma cell lines A549 and H460 and that of the two chemotherapy drugs, paclitaxel was responsible for this synergistic effect. Furthermore, the percentage of apoptotic cells was decreased with increasing rates of nobiletin to paclitaxel and carboplatin. These findings were considered to be attributed to the ability of nobiletin to regulate cells in the G(1) phase, which escaped cell death initiated by paclitaxel and carboplatin. An antitumor activity assay showed that this combination significantly suppressed the growth of subcutaneous A549 tumor xenografts in nude mice.

DOI： 10.1055/s-0034-1368321

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DOI： 10.1007/s11418-012-0727-y

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DOI： 10.1007/s11418-012-0727-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3(-/-) mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3(-/-) mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3(-/-) mice. Lipid metabolism disorders in Sik3(-/-) mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice.

DOI： 10.1371/journal.pone.0037803

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

New orally bioavailable 5-(thiophen-2-yl)-substituted 2-aminobenzamide-series histone deacetylase inhibitors were synthesized. These compounds possess a morpholine or piperadine-derived moiety as an aqueous soluble functional group. Among them, 8b, having a 4-ethyl-2,3-dioxopiperazine-1-carboxamide group as a surface recognition domain, showed promising inhibitory activities against HCT116 cell growth and HDAC1/2. Notably, unlike MS-275, this compound did not induce apoptosis in the cell cycle tests. We therefore conducted antitumor tests of 8b and MS-275 against HCT116 cell xenografts in nude mice. Compound 8b reduced the volume of tumor mass to T/C: 60% and 47% at 45 and 80 mg/kg over 16 days, respectively. These values were comparable to the rate (T/C: 51% at 45 mg/kg) for MS-275. Furthermore, 8b, at neither 45 nor 80 mg/kg, induced the weight loss which was observed in the mice given MS-275 at 45 mg/kg. (c) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2012.01.053

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

Histone deacetylase inhibitor (HDACI), suberoylanilide hydroxamic acid (SAHA), approved by the Food and Drug Administration (FDA) for the treatment of cutaneous T cell lymphoma, is a promising new treatment strategy for various cancers. In this study, we hypothesized that a liposomal formulation of HDACI might efficiently deliver HDACI into tumors. To incorporate HDACI efficiently into the liposomal membrane, we synthesized six HDACI-lipid conjugates, in which polyethylene glycol(2000) (PEG(2000))-lipid or cholesterol (Chol) was linked with a potent hydroxamic acid, HDACI, SAHA or K-182, by cleavable linkers, such as ester, carbamide and disulfide bonds. Liposomal HDACI-lipid conjugates were prepared with distearoylphosphatidylcholine (DSPC) and HDACI-Chol conjugate or with DSPC, Chol and HDACI-PEG-lipid conjugates, and their cytotoxicities were evaluated for human cervix tumor HeLa and mouse colon tumor Colon 26 cells. Among the liposomes, liposomal oleyl-PEG(2000)-SAHA conjugated with SAHA and oleyl-PEG(2000) via a carbamate linker showed higher cytotoxicity via hyperacetylation of histone H3 and induction of caspase 3/7 activity. These results suggested that liposomal HDACI-lipid conjugates may be a potential tool for cancer therapy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0026148

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

Arctiin and its aglucone, arctigenin from the fruits of Arctium lappa L. showed potent in vitro antiviral activities against influenza A virus (A/NWS/33, H1N1) (IFV). Based on the data from time-of-addition experiments and on release tests of progeny viruses, arctigenin was assumed to interfere with early event(s) of viral replication after viral penetration into cells, and to suppress the release of progeny viruses from the host cells. Arctiin was orally effective against either IFV-inoculated normal or 5-fluorouracil (5-FU)-treated mice, being less effective as compared with oseltamivir. Noticeably, arctiin produced a larger amount of virus-specific antibody than those of control and oseltamivir in sera collected from 5-FU-treated mice. Furthermore, oral treatment of 5-FU-treated mice with arctiin did not induce any resistant viruses, although the same treatment with oseltamivir induced resistant viruses at a 50% frequency. When the combination of arctiin and oseltamivir was administered to normal mice infected with IFV, the virus yields in both bronchoalveolar lavage fluids and lungs were significantly reduced relative to those in the mice treated with arctiin or oseltamivir alone. Thus, monotherapy of arctiin or combined therapy of arctiin with oseltamivir would be another treatment option for influenza.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

New 2-aminobenzamide-type histone deacetylase (HDAC) inhibitors were synthesized. They feature a sulfur-containing bicyclic arylmethyl moiety-a surface recognition domain introduced to increase in cellular uptake-and a substituted tert-amino group which affects physicochemical properties such as aqueous solubility. Compound 22 with a (2-hydroxyethyl)(4-(thiophen-2-yl)benzyl)amino group reduced the volume of human colon cancer HCT116 xenografts in nude mice to T/C 67% by oral administration at 45 mg/kg, which was comparable to the rate (T/C 62%) for a positive control, MS-275. Western blot analyses as well as cell cycle and TUNEL assays by flow cytometry suggested that the two compounds inhibited the growth of cancer cells via similar mechanisms. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmc.2010.04.033

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATL ACAD SCIENCES  

Engineered protein pores have several potential applications in biotechnology: as sensor elements in stochastic detection and ultrarapid DNA sequencing, as nanoreactors to observe single-molecule chemistry, and in the construction of nano- and micro-devices. One important class of pores contains molecular adapters, which provide internal binding sites for small molecules. Mutants of the alpha-hemolysin (alpha HL) pore that bind the adapter beta-cyclodextrin (beta CD) similar to 10(4) times more tightly than the wild type have been obtained. We now use single-channel electrical recording, protein engineering including unnatural amino acid mutagenesis, and high-resolution x-ray crystallography to provide definitive structural information on these engineered protein nanopores in unparalleled detail.

DOI： 10.1073/pnas.0914229107

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER  

We developed histone deacetylase inhibitor (HDACI) prodrugs to enhance the expression of the external genes transfected into human cells with cationic nanoparticles (NPs). We synthesized five kinds of lipid-linked HDACI prodrugs in which n-dodecanoic acid or cholesterol is linked with a potent HDACI, K-182, by an ester bond or a disulfide carbonate linker. The prodrugs were able to admix as a component of NPs, although the intact K-182 was not incorporated into NPs. Namely, NPs composed of cholesteryl-3 beta-carboxyamidoethylene-N-hydroxyethylamine and Tween 80 with the 10 mol% K-182 prodrug were prepared as a DNA vector to transfect plasmid DNAs into human prostate cancer cells, PC-3, or human breast cancer cells, Sk-Br-3. The NPs containing K-182 prodrugs with n-dodecanoic acid exhibited two to four times higher the gene expression than the original NPs. The enhancement of the gene expression will be due to the hyperacetylation of core histories caused by intact K-182 degraded from the prodrug in the vector incorporated into the cells. (C) 2009 Elsevier Masson SAS. All rights reserved.

DOI： 10.1016/j.ejmech.2009.06.036

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Aims: To measure antibacterial activity of the semi-synthetic flavonoid 3-O-octanoyl-(-)-epicatechin and investigate the mechanism of action.
Methods and Results: MICs determined by the broth microdilution method were 50 mu g ml(-1) for beta-lactam sensitive and resistant Staphylococcus aureus, and 100 mu g ml(-1) for vancomycin sensitive and resistant enterococci. In time-kill studies, 100 mu g ml(-1) 3-O-octanoyl-(-)-epicatechin reduced colony forming unit numbers of antibiotic sensitive and methicillin-resistant Staph. aureus below detectable levels within 120 min. Bacterial aggregation was not observed when cells exposed to 3-O-octanoyl-(-)-epicatechin were examined by light microscopy. It was also shown that 50 mu g ml(-1) 3-O-octanoyl-(-)-epicatechin is capable of reducing colony forming unit numbers of high cell density Staph. aureus populations by 80-fold within 60 min incubation, and inducing leakage of 50% of their internal potassium within just 10 min.
Conclusions: 3-O-Octanoyl-(-)-epicatechin is active against Gram-positive bacteria, has bactericidal activity against both antibiotic sensitive and resistant strains, and is likely to exert its primary antibacterial effect by damaging the cytoplasmic membrane.
Significance and Impact of the Study: 3-O-Octanoyl-(-)-epicatechin has significant antibacterial activity and additional structural modification and/or formulation studies may allow this to be potentiated.

DOI： 10.1111/j.1365-2672.2008.03881.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

A 2'-succinyltaxol-bovine serum albumin (BSA) conjugate was prepared as an antigen to produce an anti-taxol monoclonal antibody by immunizing mice. Formation of a linkage between hapten and protein is usually confirmed by the UV or fluorescamine method. However, it was difficult to confirm the binding of 2'-succinyltaxol to BSA by these methods owing to the similar UV absorption maxima of 2'-succinyltaxol (273 nm) and BSA (280 nm). In the present study, we therefore conducted a mass spectrometric analysis using the precursor ion scan and MS/MS techniques to confirm the formulation of the 2'-succinyltaxol-BSA conjugate in the following way: The conjugate was subjected to thermal denaturalization, dithiothreitol (DTT)-reduction, iodoacetamide-alkylation and trypsin-digestion, affording a peptide fragment mixture. This was then analyzed by electrospray ionization (ESI)-MS in the positive mode by scanning the peaks containing a mass of 854 corresponding to taxol. The detected peaks were in turn subjected to MS/MS measurements. Among them, a peak at m/z 1247.4 was found to be a peptide fragment containing Lys (epsilon-2'-succinyltaxol), demonstrating the formulation of the 2'-succinyltaxol-BSA conjugate. In order to confirm the feasibility of this analytical method, the deacetylvinblastine (deacetylVLB)-BSA antigen which produced the anti-VLB monoclonal antibody (MAb-10-A9), was subjected to the same analytical treatment as above, giving a peak at m/z 851.3 originating from a Lys (epsilon-deacetylVLB). Thus, this new method could serve as an additional tool for confirmation of the formation of hapten-protein conjugates which are difficult to detect by the above spectrophotometric methods.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-V C H VERLAG GMBH  

DOI： 10.1002/cbic.200800133

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

FTY720 (fingolimod), a novel immunosuppressant, was found to become biologically activated by phosphorylation into FTY720-1-phosphate (FTV720-P), which is a high-affinity agonist for sphingosine-1-phosphate (sphingosine-1-P)-receptors. FTY720 has also been reported to have a strong antitumor activity. The association between the phosphorylation of FTY720 and the growth inhibition of FTY720 against cancer cells are still not completely understood. In this study, we investigated the effects of FTY720, sphingosine, and their related compounds on the proliferation of human breast cancer cell lines (MCF-7, MDA-MB-231 and Sk-Br-3) and human colon cancer cell lines (HCT-116 and SW620). Non-phosphorylated FTY720, sphingosine and an FTY720 derivative, ISP-I-55, showed significant growth inhibition against these cells, with IC50 values of 5-20 mu M at 48 h postdrug treatment. We confirmed that FTY720 induces the activation of a major mitogen-activated protein kinase, JNK, without the activation of p38 and down-regulation of phospho-ERK in MCF-7 breast cancer cells. In contrast, the phosphorylated derivatives, FTY720-P and sphingosine-1-P, as well as a phosphinane FTY720 derivative, cFTY720-P, did not inhibit the growth of the cells in the concentration range of 5-50 mu M, whereas FTY720-P and sphingosine-1-P slightly induced the growth of MCF-7 cells. Combining FTY720 with dimethylsphingosine, a sphingosine kinase inhibitor, augmented the inhibitory effect of FTY720. These results indicate that the antiproliferative activity, of FTY720 does not result from its phosphorylation, either endogenous or exogenous.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

Our laboratory has been investigating the use of compounds which disrupt beta-catenin/T cell factor (TCF) binding to treat human colon cancer. There are several cysteine residues on the surface of beta-catenin where it binds to TCE Some bis[2-(acylamino)phenyl] disulfides might have the ability to form a disulfide bond with the cysteine residues of beta-catenin, leading to inhibition of the growth of human colon cells. Bis[2-(acylamino)phenyl] disulfides were screened to inhibit the growth of cancer cells. Among them, bis[2-(2,2-dimethylpropanoylamino)phenyl] disulfide (1) had promising inhibitory effects (HCT116, IC50: 9.7 mu M; DLD-1, IC50: 6.9 mu M) on cell proliferation, and did not show any cytotoxicity among normal human fibroblast CCD-1059SK cells even at 200 mu M. This derivative reduced the beta-catenin/TCF4 association in the HCT116 cells to ca. 50% at 150,mu M. Furthermore, it activated markedly the phosphorylation of c-Jun N-terminal kinase (JNK) connected to stress-activated apoptosis at a lower concentration (30 mu M). In view of cell cycle analyses, Hoechst staining, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin Nick end-labeling (TUNEL) assays along with the above results, it is likely that 1 inhibited the growth of HCT116 cells through pathways including the JNK-mediated apoptosis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

We compared anti-proliferative activities of (-)-epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) against HCT116 colorectal carcinoma cells. These catechins inhibited cell growth to nearly the same extent at low, cell confluency in plates. However, their inhibitory effect grew weaker as cell confluence increased, and this tendency was more conspicuous for EGC than for EGCG. Both EGCG and EGC activated the phosphorylation of the major MAPKs, ERK, JNK, and p38, in the HCT116 cells as in many other established human cancer cells though to different extents. Cell cycle analyses, DNA fragmentation assays, and TUNEL assays as well as Western blot assays suggested that these catechins inhibited cell growth through mitogen-activated protein kinase (MAPK)-mediated apoptosis rather than cell cycle regulation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE SA  

Alamethicin forms voltage-gated ion channels that have moderate cation-selectivity. The enhancement of the cation-selectivity by introducing negatively charged residues at positions 7 and 18 has been studied using the tethered homodimers of alamethicin with Q7 and E18 (di-alm-Q7E18) and its analog with E7 and Q18 (di-alm-E7Q18). In the dimeric peptides, monomer peptides are linked at the N-termini by a disulfide bond. Both the peptides formed long lasting ion channels at cis-positive voltages when added to the cis-side membrane. Their long open duration enabled us to obtain current-voltage (I-V-m) relations and reversal potentials at the single-channel level by applying a voltage ramp during the channel opening. The reversal potentials measured in asymmetric KCl solutions indicated that ionized E7 provided strong cation-selectivity, whereas ionized E18 little influenced the charge selectivity. This was also the case for the macroscopic charge selectivity determined from the reversal potentials obtained by the macroscopic I-V-m measurements. The results are accounted for by stronger electrostatic interactions between permeant ions and negatively charged residues at the narrowest part of the pore than at the pore mouth. (c) 2006 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.bioelechem.2006.05.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Berberine chloride (1) and the structurally related compounds were assessed for the anti-human cytomegalovirus ;(HCMV) activity using the plaque assay. The anti-HCMV activity (IC50 0.68 mu M) of 1 was equivalent to that (IC50 0.91 mu m) of ganciclovir (GCV). The mechanism of action by which I inhibits the replication of HCMV is presumed to be different from that of GCV; 1 would interfere with intracellular events after virus penetration into the host cells and before viral DNA synthesis. (c) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2006.12.085

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER  

New series historic deacetylase inhibitors comprising a hydroxamic acid or 2-aminobenzamide group as a zinc-chelating function were synthesized and evaluated for antiproliferative activities against a panel of human cancer cells. The 2-aminobenzamide series inhibitors generally had the potency in cell growth inhibitions comparable to that of MS-275. Among them, the compound having a (3,4-difluorobenzyl)(2-hydroxyethyl) amino group at one end and a 2-aminobenzamide group at the other of molecule showed the most promising profile as an anticancer drug candidate, since it had a comparatively low toxicity as did MS-275 against a normal fibroblast cell CCD-1059SK. Additionally, the derivative exhibited a high recovery in human plasma stability test. (c) 2006 Elsevier SAS. All rights reserved.

DOI： 10.1016/j.ejmech.2006.02.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

Dimeric indole alkaloid, anhydrovinblastine, which can be obtained from catharanthine and vindoline in a high yield, was converted stereoselectively into vinblastine through alternating oxidation-reduction with oxygen and NaBH3CN in the presence of anti-vinblastine monoclonal antibody.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurological disorder caused by a CAG repeat expansion in the DRPLA gene encoding polyglutamine, (polyQ). Although previous experimental studies have demonstrated that histone deacetylase (HDAC) inhibitors are therapeutically active, known HDAC inhibitors have considerable adverse effects clinically. To identify new HDAC inhibitors for the treatment of DRPLA, we evaluated a new series of HDAC inhibitors, N-hydroxycarboxamides des, with our drug screening system, which uses neuronal PC12 cells stably transfected with a part of the DRPLA gene. We found that two of four N-hydroxycarboxamides significantly reduced polyQ-induced cell death. The essential structure of these compounds is a hydroxamic acid residue, which is shared with trichostatin A, a known HDAC inhibitor. Although our study showed mild neuroprotective effects, further structural modification of compounds that retain this residue may decrease cytotoxicity and increase protective activity against polyQ toxicity. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2005.09.019

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

Two compounds were synthesized which have a structural component other than those of our new series histone deacetylase (HDAC) inhibitors to determine the structure-activity relationship. It was also examined whether the inhibitory effects on cancer cell proliferation by HDAC inhibitors involve p21/WAF1 induction and G(1) or G(2)/M arrest in p53-mutated MG63 human osteosarcoma cells as do other HDAC inhibitors. It was demonstrated that inhibitors with the 2-naphthylcarbonyl group and hydroxamic acid at both termimal sides as well as the phenylene component at the center of molecule markedly induce the p21/WAF1 protein by stimulating p21/WAF1 gene promoter activity. Furthermore, cell cycle analysis revealed that these compounds arrest MG63 cells in the G(2)/M phase.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

Two compounds were synthesized which have a structural component other than those of our new series histone deacetylase (HDAC) inhibitors to determine the structure-activity relationship. It was also examined whether the inhibitory effects on cancer cell proliferation by HDAC inhibitors involve p21/WAF1 induction and G(1) or G(2)/M arrest in p53-mutated MG63 human osteosarcoma cells as do other HDAC inhibitors. It was demonstrated that inhibitors with the 2-naphthylcarbonyl group and hydroxamic acid at both termimal sides as well as the phenylene component at the center of molecule markedly induce the p21/WAF1 protein by stimulating p21/WAF1 gene promoter activity. Furthermore, cell cycle analysis revealed that these compounds arrest MG63 cells in the G(2)/M phase.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER CHEMICAL SOC  

Recently, 3-O-octanoyl-(+)-catechin (OC) was synthesized from (+)-catechin (C) by incorporation of an octanoyl chain into C in the light of (-)-epicatechin gallate (ECg) and (-)-epigallocatechin gallate (EGCg), which are the major polyphenols found in green tea and have strong physiological activities. OC was found to inhibit the response of ionotropic gamma-aminobutyric acid (GABA) receptors (GABA(A) receptors) and Na+/glucose cotransporters expressed in Xenopus oocytes in a noncompetitive manner more strongly than does C. OC also induced a nonspecific membrane current and decreased the membrane potential of the oocyte, and thus death of the oocyte occurred even at lower concentrations than that induced by C or EGCg. Although EGCg produced H2O2 in aqueous solution, OC did not. This newly synthesized catechin derivative OC possibly binds to the lipid membrane more strongly than does C, Ecg, or EGCg and as a result perturbs the membrane structure.

DOI： 10.1021/jf048492c

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記述言語：英語   出版者・発行元：日本生薬学会  

(-)-Epigallocatechin (EGC) and its acylated derivatives, 3-O-octanoyl-(-)-EGC and 3-O-[(RS)-2-methyloctanoyl]-(-)-EGC, were examined by oral administration for the suppression effect on the two stage mouse skin carcinogenesis which were induced by NO as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter. Although there was no significant difference in the effect among these catechins, they all suppressed papilloma formation compared with the control at the following overwhelming rates: 90.1% for (-)-EGC, 85.2% for 3-O-octanoyl-(-)-EGC and 8 1.5 % for 3-O-[(R.S)-2-methyloctanoyl]-(-)-EGC. It was thus deduced that (-)-EGC can be an orally active candidate for tumor chemoprevention.

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その他リンク： http://dl.ndl.go.jp/info:ndljp/pid/10760280

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記述言語：英語   出版者・発行元：日本生薬学会  

科研費基盤研究

CiNii Books

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その他リンク： http://dl.ndl.go.jp/info:ndljp/pid/10760280

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

The screening tests of N-hydroxybenzamides for their HDAC-inhibitory activities led to the discovery of the promising compounds with a 2-naphthylcarbonyl group and with a 1,4-biphenylcarbonyl group. These compounds were further modified to optimize their physico-chemical profile. As a result, the inhibitor with a 6-amino-2-naphthylcarbonyl was obtained, which showed not only promising growth inhibitions against a panel of tumor cells, but also an improved water solubility. It exhibited the maximal 185% of survival rate (%T/C) in a in vivo experiment with P388 cell-inoculated mice. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmc.2004.06.020

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DOI： 10.1016/j.ijantimicag.2004.03.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

In the course of an exploratory investigation of antitumor-promoting catechins, 3-O-acyl-(+)-catechins of varying carbon lengths from C-4 to C-18 were assessed for inhibitory effects on the activation of the Epstein-Barr virus early antigen. Like 3-O-acyl-(-)-epigallocatechins, the (+)-catechin derivatives showed promising effects with the C-3 acyl chain of C-8-C-11 carbon atoms.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

In order to seek promising cancer chemopreventive agents, we assessed the antitumor promoting activities of 3-O-octanoyl or 3-O-(2-methyloctanoyl)-(-)-epigallocatechins, inhibiting markedly the activation of Epstein-Barr virus early antigen, in a two-stage mouse skin carcinogenesis assay. As a result, these derivatives inhibited a papilloma formation 1.3-1.6-fold more strongly than (-)-epigallocatechin gallate well established as anti-tumor promoter. (C) 2003 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmc.2003.08.016

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOPHYSICAL SOCIETY  

A covalent dimer of alamethicin Rf30 was synthesized by linking the N-termini by a disulfide bond. When the dimer peptides were added to the cis-side of a diphytanoyl PC membrane, macroscopic channel current was induced only at cis positive voltages. The single-channel recordings showed several conductance levels that were alternately stabilized. These results indicate that the dimer peptides form stable channels by N-terminal insertion like alamethicin and that most of the pores are assembled from even numbers of helices. Taking advantages of the long open duration of the dinner peptide channels, the current-voltage (I-V) relations of the single-channels were obtained by applying fast voltage ramps during the open states. The I-V relations showed rectification, such that current from the cis-side toward the trans-side is larger than that in the opposite direction. The intrinsic rectification is mainly attributed to the macro dipoles of parallel peptide helices surrounding a central pore.

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科研費基盤研究

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

The asymmetric reaction of omega-oxo-alpha,beta-unsaturated esters with lithium chiral thiolates afforded the Michael-aldol tandem cyclization products in high yield and good stereo selectivity. Reductive desulfurization gave the corresponding optically pure 2-hydroxycycloalkanecarboxylates. (C) 2003 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0040-4039(03)00253-3

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科研費基盤研究

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記述言語：英語   出版者・発行元：日本生薬学会  

科研費基盤研究

CiNii Books

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その他リンク： http://dl.ndl.go.jp/info:ndljp/pid/10760015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

In order to seek a urease inhibitor more potent than hydroxyurea (1), its alkyl- or phenyl-substituted derivatives were synthesized and evaluated for their effect on the jack bean urease. Of 16 compounds tested, m-methyl(10) and m-methoxy-phenyl substituted hydroxyurea (13) showed the most potent inhibitory activities against the enzyme.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Upon successive treatment with lithium diisopropylamide and then benzaldehyde, a chiral α,β,ψ,ω- unsaturated bisphosphine oxide underwent Michael cyclization-aldol tandem reaction to afford the corresponding endo- α,β-unsaturated cyclic bisphosphine oxides. Sequential stereoselective reduction and Horner-Wadsworth-Emmons olefination gave the corresponding monophosphine oxide. Oxidative conversion of an olefin moiety into a carboxyl group and subsequent deoxygenation of an oxide gave the corresponding chiral phosphinocarboxylic acid, which was successfully applied as a chiral and functionalized monophosphine ligand in a palladium-catalyzed asymmetric allylic alkylation.

DOI： 10.1021/jo025725v

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PubMed

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記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

Grant-in-Aid for Scientific Research 200004-200303

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

DOI： 10.1080/10426500290094666

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOPHYSICAL SOCIETY  

To evaluate the role of charged residues facing a pore lumen in stability of channel structure and ion permeation, we studied electrical properties of ion channels formed by synthesized native alamethicins (Rf50 (aim-Q7Q18) and Rf30 (aim-Q7E18)) and their analogs with Glu-7 (alm-E7Q1 8 and alm-E7E18). The single-channel currents were measured over a pH range of 3.5 to 8.7 using planar bilayers of diphytanoyl PC. The peptides all showed multi-level current fluctuations in this pH range. At pH 3.5 the channels formed by the four peptides were similar to each other irrespective of the side chain differences at positions 7 and 18. The ionization of Glu-7 (E7) and Glu-18 (E18) above neutral pH reduced the relative probabilities of low-conductance states (levels 1 and 2) and increased those of high-conductance states (levels 4-6). The channel conductance of the peptides with E7 and/or E18, which was distinct from that of aim-Q7Q18, showed a marked pH-dependence, especially for low-conductance states. The ionization of E7 further reduced the stability of channel structure, altered the current-voltage curve from a superlinear relation to a sublinear one, and enhanced cation selectivity. These results indicate that ionized E7 strongly influences the channel structure and the ion permeation, in contrast to ionized E18.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

Mono- and di-substituted allenes 5 were synthesized by successive Horner-Wadsworth-Emmons olefination starting from methylene-bisphosphonate 1 and two carbonyl compounds. The key to success is KH or KH-18-crown-6 as a base for the second HWE olefination of hydroxyalkenylphosphonates 4.

DOI： 10.1080/10426500290093432

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Conjugate reduction-initiated cyclization of a chiral alpha,beta,chi,psi-unsaturated bisphosphine oxide,as developed by treating with lithium tri-siamylborohydride (LS-selectride") Lis a reducing agent to afford efficiently and selectively a carbocycle bearing bisphosphine appendage. (C) 2002 Elsevier Science Ltd. All rights reserved.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Utilizing tranexamic acid as a starting material, a series of N-hydroxycarboxamides were synthesized in order to seek new histone deacetylase (HDAC) inhibitors. Further structure optimization involving the replacement of the 1,4-cyclohexylene group with the 1,4-phenylene group yielded the promising HDAC inhibitors which possess a terminal bicyclic aryl amide. (C) 2002 Elsevier Science Ltd. All rights reserved.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

LDA treatment of aldehydes or ketone with alkenylphosphonates 2, prepared by Horner-Wadsworth-Emmons (HWE) reaction of methylenebisphosphonate I with aldehydes, afforded Baylis-Hillman reaction-type products 5 in high yields. HWE olefination of 5 with KH or KH-18-crown-6 as a base provided allenes in good yields. One-flask procedure was successfully developed starting from I to afford an allene in a reasonably good yield. (C) 2002 Elsevier Science Ltd. All rights reserved.

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科研費基盤研究 200004-200303

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科研費基盤研究 200004-200303

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科研費基盤研究 200004-200303

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ROYAL SOC CHEMISTRY  

Upon treatment with lithium diisopropylamide achiral and chiral alpha,beta,psi,omega-unsaturated bisphosphine oxides underwent lithiation-conjugate addition tandem cyclization to afford the corresponding endo-alpha,beta-unsaturated cyclic bisphosphine oxides; sequential stereoselective reduction of the cyclized bisphosphine oxide gave the corresponding trans- and cis-bisphosphines that were successfully applicable in a catalytic asymmetric hydrogenation as chiral bisphosphine ligands.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER CHEMICAL SOC  

(-)-Neplanocin A (1), S-adenosylhomocystein hydrolase inhibitor, was synthesized. The characteristic of this synthesis is a stereoselective construction of five-membered ring of neplanocin A by intramolecular aldol reaction of the lithium enolate that was generated by conjugate addition of lithium thiolate. TBS-protected chiral omega -oxo-alpha,beta -unsaturated ester 16, which was prepared from D-mannitol, was treated with 1.2 equiv of lithium benzylthiolate in THF at -20 degreesC to give three separable cyclization products in good yields and stereoselectivity. After conversions of protective groups, the benzylsulfanyl part of 21 was removed by oxidation to sulfoxide and subsequent thermal elimination to give the requisite double bond. Through the functional group transformations of 30, total synthesis of (-)-neplanocin A (1) was accomplished.

DOI： 10.1021/jo016090n

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Chemical Society (ACS)  

DOI： 10.1021/ja0169318

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER CHEMICAL SOC  

A reaction mode of imines derived from naphthalene-1-carbaldehyde and acyclic alpha,beta -unsaturated aldehydes with organolitium reagents was dependent on the characteristic nature of a substituent on the imine nitrogen atom. An imine having an electron-withdrawing aryl group on the nirtogen atom behaves as a 1,2-directing imine toward organolithium reagents. In contrast, an imine bearing an alkyl or a bulky aryl group favors 1,4-addition of organolithium reagents. Electronic and steric tuning of a substituent on the imine nitrogen atom for a reaction mode was rationalized on the basis of molecular orbital calculations.

DOI： 10.1021/jo015766b

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記述言語：日本語   出版者・発行元：天然有機化合物討論会  

(-)-Neplanocin A is a carbonucleoside isolated from Ampullariella regularis in 1981, and have a S-adenosylhomocystein hydrolase inhibitory activity. Until today, several examples of the total synthesis were reported. However, there is no precedent of the total synthesis using intra-molecular aldol reaction for ring construction of neplanocin A. During the course of our studies on development of asymmetric reaction, we have already developed a lithium thiolate-catalyzed stereoselective Michael-aldol tandem reaction of α,β-unsaturated esters with aldehydes. We describe here a development of lithium thiolate-initiated Michael-aldol tandem cyclization reaction as an extension of intermolecular tandem reaction, and a total synthesis of (-)-neplanocin A by using the present cyclization as a key reaction for construction of five-membered ring. The reaction of ω-oxo-α,β-unsaturated ester 6 with 0.2 equiv of lithium thiophenolate (PhSLi) in the presence of 2 equiv of phenyl trimethylsilyl sulfide (PhSTMS) in THF at 0℃ for 2h gave cyclization products 7a and 7b in 61% and 18% yields, respectively. The presence of PhSTMS, which traps lithium alkoxide as a stable TMS ether, was essential for both high yield and stereoselectivity. High yield and stereoselectivity was also obtained by using lithium benzylthiolate (BnSLi) as a nucleophile which has higher nucleophilicity than that of PhSLi. The reaction of 6 with 1.2 equiv of BnSLi in THF at -20℃ proceeded within 1h to give cyclization product 11 in 95% yield as a sole product. We applied this cyclization reaction to total synthesis of (-)-neplanocin A. TBS-protected chiral ω-oxo-α,β-unsaturated ester 23, which was derived from D-mannitol, was treated with 1.2 equiv of BnSLi in THF at-20℃ for 0.5 h to give three separable cyclization products 24a, 24b and 25 in 34%, 28% and 11% yields, respectively. After conversions of protective groups, the benzylsulfanyl part of 29 was removed by oxidation to sulfoxide and subsequent thermal elimination. Through the functional group transformations of 30, we have achieved a total synthesis of (-)-neolanocin A.

DOI： 10.24496/tennenyuki.43.0_205

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科研費基盤研究 200004-200303

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科研費基盤研究 200004-200303

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-V C H VERLAG GMBH  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ROYAL SOC CHEMISTRY  

Activation of diethyl phosphate was realized by attaching trifluoromethanesulfonanilide as an efficient leaving group and the phosphate 1 proved to be a promising amide and peptide coupling reagent.

DOI： 10.1039/b0042641

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER CHEMICAL SOC  

[GRAPHICS]
The reaction of alpha,beta,psi,omega-unsaturated bisphosphonates 1 with organolithiums afforded conjugate addition-Michael tandem cyclization products 3 and deprotonation-Michael cyclization products 5. Highly stereoselective deuteration of the intermediates proved the stereochemistry of lithium phosphonates 10, 13, and 15.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

The reaction of omega-oxo-alpha,beta-unsaturated esters with lithium thiolates afforded the Michael-aldol tandem cyclization products in good to perfect stereoselectivity depending on the nature of thiolates. (C) 1999 Elsevier Science Ltd, All rights reserved.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ROYAL SOC CHEMISTRY  

N-Benzyloxy- and N-tert-butoxycarbonyltrifluoromethylsulfonyl-4-trifluoromethylanilides were prepared and were found to be chemoselective and shelf-storable alkoxycarbonylation reagents.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Reactions of alpha,beta-unsaturated esters with aldehydes were catalyzed by 0.2 equiv of lithium benzenethiolate in the presence of phenyl trimethylsilyl sulfide to afford the conjugate addition-aldol tandem reaction products in the anti stereoselectivity and good to high yields. (C) 1999 Elsevier Science Ltd. All rights reserved.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

We examined membrane fluidity of bovine adrenal chromaffin cells and chromaffin granules using cationic trimethylammonium derivative of diphenylhexatriene (TMA-DPH) as a fluorescence probe. After adding TMA-DPH to the suspension of chromaffin cells and that of granules, it first bound to the outer layer of the plasma membrane of the dells and that of the granule membrane, then gradually penetrated the inner layer of each membrane and distributed to both leaflets of the respective membranes. Accompanying increases in the ratio of incorporated probe on the cytoplasmic side of the chromaffin cell membrane, its fluorescence anisotropy gradually decreased. However, in chromaffin granules,the fluorescence anisotropy gradually increased with increases in the ratio of incorporated probe. These findings suggest that the inner layer of the plasma membrane and outer layer of the granular membrane are more fluid than the corresponding side of each membrane, which is suitable for the fusion between both membranes. We also examined the effect of trichosporin-B VIa, a fungal ion channel forming alpha-aminoisobutyric acid-containing peptide, on the fluidity of chromaffin cells using TMA-DPH. The peptide decreased the fluorescence anisotropy and increased the fluorescence intensity in the concentration range that induced Ca2+ dependent catecholamine secretion, suggesting that a change in lipid dynamics of the lipid bilayer of the plasma membrane was induced by this peptide. (C) 1998 Elsevier Science B.V. All rights reserved.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Two types of external, chiral amidophosphine ligands, 1-5, were prepared. Examination of their behavior in an asymmetric conjugate addition reaction of organocuprate revealed the possibility for steric tuning to realize high selectivity. (C) 1998 Elsevier Science Ltd. All rights reserved.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER CHEMICAL SOC  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Three types of an external, chiral amide ligand, 2-6, were prepared and examination of their behavior in an asymmetric conjugate addition reaction of lithium dimethylcuprate with chalcone revealed the possibility for steric tuning to realize high selectivity. Copyright (C) 1996 Elsevier Science Ltd.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Trichosporin-B-VIa (TS-B-VIa) has a Pro(14)-kinked helical structure which is considered to be important for the formation of peptaibol-type ion-channels in lipid bilayer membranes. TS-B-VIa and its analog [Aib(14)]TS-B-VIa with Pro --> Aib substitution at position 14, resulting in a straight helical structure, were tested for ion-channel-forming activity in planar lipid bilayer membranes and for ability to induce catecholamine secretion from cultured bovine adrenal chromaffin cells. Voltage-dependent multi-channel conductance, which is characteristic of TS-B-VIa, was also observed for [Aib(14)]TS-B-VIa. In single-channel measurements, current fluctuations induced by [Aib(14)]TS-B-Vla had a shorter life-time and showed fewer substates than those induced by TS-B-VIa. Catecholamine secretion induced by these peptides at low concentrations is completely Ca2+-dependent. At high concentrations, TS-B-VIa-induced secretion was partly independent of external Ca2+, but this was not the case for the analog. The differences of behavior can be explained in terms of the differences of hydrophobicity, amphiphilicity, and magnitude of dipole moment due to the conformational changes around position 14 and the C-terninal domain caused by the Pro --> Aib substitution.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ROYAL SOC CHEMISTRY  

Replacement of the Gln(7) residue, which is well conserved among ion-channel-forming peptaibols, by an Ala in trichosporin-B-VIa (TS-B-VIa = AcUAUAUUQUIUGLUPVUUQQPheol; U = alpha-aminoisobutyric acid, Pheol = phenylalaninol) alters neither the multilevel nature of the TS-B-VIa channel nor its conductance, but abolished the rectification of the membrane current characteristic of the TS-B-VIa channel.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOHN WILEY & SONS LTD  

The mass spectral characteristics of selected peptaibols were investigated using electrospray ionization in conjunction with low-energy collision-induced dissociation (CID). Protonated and sodiated molecular species were selected as precursor ions and the resulting CID spectra are discussed with respect to fragmentation characteristics related to the structures of peptaibols. The CID spectra of peptaibols with acetylated N-terminus and with the sub-sequences of Aib-Pro were similar. The CID spectra of [M + 2Na](2+) provided structural information more than those of [M + 2H](2+) and [M + H + Na](2+). The CID of [M + 2Na](2+) can be used to deduce complete sequence information for peptaibols.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ROYAL SOC CHEMISTRY  

Examination of newly synthesized elongated and truncated analogues of the ion-channel-forming peptide, trichosporin-B-Vla (20 residues), for ion-channel-forming activity in lipid bilayer membranes and catecholamine secretion-inducing activity from adrenal chromaffin cells revealed that the natural compound has the optimal molecular length for both activities.

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記述言語：英語   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

Trichosporin (TS)-B-VIa, a peptide consisting of 19 amino acid residues and an amino alcohol, causes Ca2+-dependent secretion of catecholamines from bovine adrenal chromaffin cells. The TS-B-VIa-induced secretion was greater under alkaline conditions and at a temperature of 37 degrees C compared with that at 21 degrees or 30 degrees C. It was not observed when the peptide was eliminated from the incubation medium. These results strongly suggest that the stimulatory effect of TS-B-VIa on the secretion is reversible and dependent on the temperature and pH of the incubation medium.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

The secondary structures of an ion-channel-forming icosapeptaibol, trichosporin B-VIa, and its Aib(14)-substituted derivative containing no Pro were investigated on the basis of CD and various NMR experiments in methanol, Trichosporin B-VIa has a fully helical structure with a kink stabilized by a 1<--4 hydrogen-bond between the Leu(12) CO and Val(15) NH, The helical structure is composed of 3(10)-helix in the N-terminal first turn and the C-terminal moiety following Leu(12), and a-helix in the middle region, In contrast, the Aib(14) derivative predominantly has a straight a-helical structure except for a 3(10)-helix region in the N-terminal first turn.

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：PROTEIN RESEARCH FOUNDATION  

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：PROTEIN RESEARCH FOUNDATION  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A series of peptaibols, trichosporin (TS) -Bs, induced voltage-activated conductance in lipid bilayer membranes and catecholamine secretion from bovine adrenal chromaffin cells. The order of activities is the same as that of the lipophilicity rank of TS-Bs derived from the reversed-phase HPLC capacity factors. © 1995, The Pharmaceutical Society of Japan. All rights reserved.

DOI： 10.1248/bpb.18.640

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PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

A membrane-modifying peptide antibiotic, trichosporin B-VIa, having catecholamine secretion-inducing activity on bovine adrenal chromaffin cells has been synthesized. Aib(14)-Trichosporin B-Vla, in which Pro(14) was replaced by Aib, has also been synthesized to modify the secondary structure of trichosporin B-VIa. Sequence-specific H-1-NMR assignments of both peptides in methanol were achieved by using two-dimensional NMR techniques.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

Hypelcin B is a mixture of antibiotic peptides produced by Hypocrea peltata. Hypelcins B-I, B-II, B-III, B-IV and B-V are components of this mixture purified by reversed-phase high-performance liquid chromatography. The amino acid sequences of these peptides were determined by electrospray mass spectrometry and electrospray mass spectrometry/mass spectrometry. The molecular weights of these peptides were all ca. 2000 and the structures were very similar.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

The effect of the trichosporin-Bs, peptide antibiotics, on the respiration of mitochondria was investigated. Trichosporin-Bs stimulated the respiratory rate of state 4 rat liver mitochondria in a dose-dependent manner. The maximum respiratory rate obtained by trichosporin-Bs was essentially the same as for 2,4-dinitrophenol and SF6847. Trichosporin-B-VIb released oligomycin-inhibited respiration of mitochondria. This means that trichosporin-Bs are uncouplers of oxidative phosphorylation. The stimulatory effect of trichosporin-B-VIb, a component of trichosporin-Bs, on mitochondrial respiration was increased by inorganic phosphate but not by other permeant anions studied. These results suggest that the stimulation of mitochondrial respiration by trichosporin-B-VIb is mediated by the same mechanism as is operating in the case of hypelcins and alamethicins. Furthermore, the relative potencies of trichosporin-Bs on the mitochondrial respiration and their relative hydrophobicities were examined. A clear relationship was observed between the uncoupling potencies of trichosporin-Bs and their relative hydrophobicities.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

6-Methoxy-5,8-quinolinediones (14-19) and 8-methoxy-5,6-quinolinediones (20-25) were synthesized by oxidative demethylation of the corresponding 5,6,8-trimethoxyquinolines (5, 7-9, 12, 13) with cerium (IV) ammonium nitrate.

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：PROTEIN RESEARCH FOUNDATION  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

A membrane-modifying peptide antibiotic having uncoupling activity on rat liver mitochondria, hypelcin A-III, has been synthesized by assembling five peptide fragments via the N,N'-dicyclohexylcarbodiimide method. The synthesized hypelcin A-III was identical with the natural product.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ROYAL SOC CHEMISTRY  

The secondary structure of the peptaibol trichosporin B-V in methanol was investigated in detail by 600 MHz nuclear magnetic resonance spectroscopy. Its fundamental secondary structure was characterized as a helix by the circular dichroism spectrum. Inter-residual nuclear Overhauser effect patterns, 3J(NH-CalphaH) amide coupling constants, hydrogen-deuterium (H-D) exchange rates of the amide protons, and inspection of molecular models showed that the secondary structure of this peptide consists of two major alpha-helical structures because of a bent structure around a Pro residue, and that the first three amino acid residues of the N-terminal alpha-helix are arranged predominantly in a 3(10)-helical fashion.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ROYAL SOC CHEMISTRY  

From the minor-components mixture of Trichosporin Bs (TS-Bs) produced by Trichoderma polysporum, ten components could be elucidated by means of linked-scan and continuous-flow fast-atom bombardment. The combination of their complementary results made the rapid structure elucidation of the minor components possible without isolation and purification. The identified compounds are antibiotic eicosapeptides and have very similar structures with relative molecular masses of approximately 2000. Four new peptide groups were found. In their structures, the first group has Gly at the amino acid position 3 in contrast to the known TS-Bs, the second one has Vxx (valine or isovaline) at position 12, and the third and the fourth ones have Ala at position 13 or 17, respectively.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ROYAL SOC CHEMISTRY  

Sequence-specific H-1- and C-13-nuclear magnetic resonance assignments of an antibiotic peptide, trichosporin B-V isolated from fungus Trichoderma polysporum, were achieved in methanol by using two-dimensional NMR techniques. The H-1 NMR spectra recorded at various concentrations (1-60 mmol dm-3) suggested that the peptide behaves predominantly as a monomer in methanol and that its conformation is not affected by its concentration. Furthermore, complete or partial H-1-resonance assignments of trichosporin B-Ia, -IIIa, -IVd and -VIb were carried out similarly. Comparison of the H-1 NMR parameters for the amide groups of trichosporin Bs suggested that their backbone conformations are very similar to each other. It is proposed that the significant differences in the biological activity of trichosporin Bs result from the lipophilicity of the individual molecules.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The secondary structure of the peptaibol trichosporin B-V in methanol was investigated in detail by 600 MHz nuclear magnetic resonance spectroscopy. Its fundamental secondary structure was characterized as a helix by the circular dichroism spectrum. Inter-residual nuclear Overhauser effect patterns, 3JNH-CαH amide coupling constants, hydrogen-deuterium (H-D) exchange rates of the amide protons, and inspection of molecular models showed that the secondary structure of this peptide consists of two major α-helical structures because of a bent structure around a Pro residue, and that the first three amino acid residues of the N-terminal α-helix are arranged predominantly in a 310-helical fashion.

DOI： 10.1039/p19930000375

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILLIAMS & WILKINS  

We examined the effect of trichosporin-B-III, an alpha-aminoisobutyric acid-containing antibiotic peptide consisting of 19 amino acid residues and a phenylalaninol, on catecholamine secretion from cultured bovine adrenal chromaffin cells. Incubation of the cells with trichosporin-B-III (3-20-mu-M) caused an increase in the secretion of catecholamines. The secretion induced by trichosporin-B-III at low concentrations (3 and 5-mu-M) was completely dependent on external Ca2+, whereas that induced by higher concentrations (10 and 20-mu-M) was partly independent of Ca2+. Trichosporin-B-III at low concentration (5-mu-M) did not increase the release of lactate dehydrogenase, a marker enzyme of cytoplasm, from the cells. In contrast, the peptide at higher concentration (10-mu-M) increased the release of the enzyme. Trichosporin-B-III also caused both Ca-45(2+) influx into the cells and an increase in the intracellular free Ca2+ concentration. The increases in catecholamine secretion and Ca-45(2+) influx behaved similarly in relation to trichosporin-B-III concentration (3-10-mu-M). The time courses of the increases in secretion, Ca-45(2+) influx, and intracellular free Ca2+ concentration induced by trichosporin-B-III were also quite similar. Trichosporin-B-III-induced (at 5-mu-M) secretion was not affected by the elimination of Na+ from the incubation medium or by the addition of tetrodotoxin, a blocker of highly selective voltage-dependent Na+ channels, or hexamethonium, a blocker of nicotinic acetylcholine receptors. On the other hand, both diltiazem (2-200-mu-M) and nicardipine (1-200-mu-M), blockers of voltage-dependent Ca2+ channels, inhibited the secretion induced by trichosporin-B-III (5-mu-M) in a concentration-dependent manner. Trichosporin-B-III-induced (at 5-mu-M) secretion also was suppressed by the addition of Mn2+ (5-mu-M) to the medium. The diltiazem (20-mu-M) inhibition of trichosporin-B-III-induced (at 5-mu-M) secretion was reversed by increasing the external Ca2+ concentration. These results indicate that trichosporin-B-III causes the secretion of catecholamines from bovine adrenal chromaffin cells by two mechanisms, Ca2+ dependent and Ca2+ independent (only at high concentrations of trichosporin-B-III). Furthermore, these results strongly suggest that trichosporin-B-III, in Ca2+-dependent secretion, activates endogenous voltage-dependent Ca2+ channels, or itself forms the channels in the membranes, and induces Ca2+ influx into the cells.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PHARMACEUTICAL SOC JAPAN  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：関西大学  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER CHEMICAL SOC  

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記述言語：日本語   出版者・発行元：(公社)日本薬学会  

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記述言語：日本語   出版者・発行元：関西大学  

CiNii Books

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER CHEMICAL SOC  

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The tridentate amino ether ligands 1 and 14 were developed through systematic structural modification of the bidentate diether ligand 2. The reaction of thiophenol with methyl crotonate was catalyzed by 14 and lithium thiophenolate to afford (S)-methyl 3-phenylthiobutanoate in 75% ee and 95% yield.

DOI： 10.1016/S0040-4039(98)00080-X

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開催地：Penang Malaysia  

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開催地：Osaka  

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開催地：熊本  

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開催地：熊本  

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開催地：熊本  

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開催地：熊本  

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開催地：同志社女子大学  

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開催地：Nice, France  

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開催地：Nice, France  

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開催地：パシフィコ横浜  

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開催地：パシフィコ横浜  

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開催地：パシフィコ横浜  

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開催地：Universiti Sains Malaysia, Penang, Malaysia  

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開催地：Universiti Sains Malaysia, Penang, Malaysia  

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開催地：Universiti Sains Malaysia, Penang, Malaysia  

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開催地：Universiti Sains Malaysia, Penang, Malaysia  

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開催地：Poitiers, France  

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開催地：Poitiers, France  

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開催地：北海道大学  

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開催地：北海道大学  

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開催地：関西大学  

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開催地：京王プラザホテル（東京）  

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開催地：Sitges, Spain  

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開催地：Sitges, Spain  

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開催地：Sitges, Spain  

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開催地：静岡  

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開催地：静岡  

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開催地：関西大学100周年会館  

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開催地：関西大学100周年会館  

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開催地：大阪  

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開催地：東京  

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開催地：東京  

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開催地：東京  

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開催地：東京  

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開催地：東京  

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開催地：東京  

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開催地：神戸  

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