論文 - 末永　聖武

Cell-morphology profiling of a natural product library identifies bisebromoamide and miuraenamide A as actin filament stabilizers

Sumiya Eriko, Shimogawa Hiroki, Sasaki Hiroaki, Tsutsumi Masato, Yoshita Keņichi, Ojika Makoto, Suenaga Kiyotake, Uesugi Motonari

ACS Chemical Biology 6 （ 5 ） 425 - 431 2011年05月

査読有り,  ISSN  1554-8929

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<p>Natural products provide a rich source of biological tools, but elucidating their molecular targets remains challenging. Here we report a cell morphological profiling of a natural product library, which permitted the identification of bisebromoamide and miuraenamide A as actin filament stabilizers. Automated high-content image analysis showed that these two structurally distinct marine natural products induce morphological changes in HeLa cells similar to those induced by known actin-stabilizing compounds. Bisebromoamide and miuraenamide A stabilized actin filaments in vitro, and fluorescein-conjugated bisebromoamide localized specifically to actin filaments in cells. Cell morphological profiling was also used to identify actinstabilizing or -destabilizing natural products from marine sponge extracts, leading to the isolation of pectenotoxin-2 and lyngbyabellin C. Overall, the results demonstrate that high-content imaging of nuclei and cell shapes offers a sensitive and convenient method for detecting and isolating molecules that target actin.</p>

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N,N′-diphenethylurea isolated from Okinawan ascidian Didemnum molle enhances adipocyte differentiation in 3T3-L1 cells

Choi Sun Sil, Cha Byung Yoon, Kagami Iida, Lee Young Sil, Sasaki Hiroaki, Suenaga Kiyotake, Teruya Toshiaki, Yonezawa Takayuki, Nagai Kazuo, Woo Je Tae

Journal of Antibiotics 64 （ 3 ） 277 - 280 2011年03月

査読有り,  ISSN  0021-8820

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Revised structure and structure-activity relationship of bisebromoamide and structure of norbisebromoamide from the marine cyanobacterium Lyngbya sp.

Sasaki Hiroaki, Teruya Toshiaki, Fukazawa Hidesuke, Suenaga Kiyotake

Tetrahedron 67 （ 5 ） 990 - 994 2011年02月

査読有り,  ISSN  0040-4020

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<p>Novel potent cytotoxic peptides bisebromoamide (1) and norbisebromoamide (2) have been isolated from the marine cyanobacterium Lyngbya sp. The planar structure of these peptides was elucidated through the extensive application of 1D and 2D NMR techniques. The absolute stereostructure of 1 was determined by chemical degradation followed by chiral HPLC analysis. Recently, Tao and co-workers achieved synthesis of bisebromoamide, and the configuration of thiazoline moiety was revised. We re-investigated the stereochemistry of thiazoline moiety of 1. The structure-activity relationships of bisebromoamide (1) were investigated with the use of natural and synthetic analogs. Furthermore, bisebromoamide (1) potently inhibited protein kinase: the phosphorylation of ERK in NRK cells by PDGF-stimulation was selectively inhibited by treatment with 10-0.1 μM of 1.</p>

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Marine natural product aurilide activates the opa1-mediated apoptosis by binding to prohibitin

Sato Shin Ichi, Murata Asako, Orihara Tsubasa, Shirakawa Takashi, Suenaga Kiyotake, Kigoshi Hideo, Uesugi Motonari

Chemistry and Biology 18 （ 1 ） 131 - 139 2011年01月

査読有り,  ISSN  1074-5521

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<p>Aurilide is a potent cytotoxic marine natural product that induces apoptosis in cultured human cells at the picomolar to nanomolar range; however, its mechanism of action has been unknown. Results of the present study showed that aurilide selectively binds to prohibitin 1 (PHB1) in the mitochondria, activating the proteolytic processing of optic atrophy 1 (OPA1) and resulting in mitochondria-induced apoptosis. The mechanism of aurilide cytotoxicity suggests that PHB1 is an apoptosis-regulating protein amenable to modulation by small molecules. Aurilide may serve as a small-molecule tool for studies of mitochondria-induced apoptosis.</p>

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Isolation and identification of potent allelopathic substances in a traditional bangladeshi rice cultivar kartikshail

Kato-Noguchi Hisashi, Salam Md Abdus, Suenaga Kiyotake

Plant Production Science 14 （ 2 ） 128 - 134 2011年

査読有り,  ISSN  1343-943X

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<p>Aqueous methanol extracts of a traditional Bangladeshi rice cultivar (Oryza sativa L. cv. Kartikshail) inhibited root and shoot growth of cress (Lepidium sativum), lettuce (Lactuca sativa), alfalfa (Medicago sativa), timothy (Phleum pratense), crabgrass (Digitaria sanguinalis), Italian ryegrass (Lolium multiflorum), barnyardgrass (Echinochloa crus-galli) and jungle rice (Echinochloa colonum). The inhibition was increased with increasing the extract concentration, which suggests that cv. Kartikshail may have growth inhibitory substances and allelopathic potential. The aqueous methanol extract of cv. Kartikshail was purified and two main inhibitory substances were isolated and identified by spectral data as 3-hydroxy-β-ionone and 9-hydroxy-4-megastigmen-3-one. The concentrations required for 50% growth inhibition on cress roots and shoots, respectively, were 4.9 and 9.5 μM for 3-hydroxy-β-ionone, and 0.54 and 0.72 μM for 9-hydroxy-4-megastigmen-3-one. The concentrations required for 50% growth inhibition on barnyardgrass roots and shoots, respectively, were 160 and 310 μM for 3-hydroxy-β-ionone, and 53 and 140 μM for 9-hydroxy-4- megastigmen-3-one. The inhibitory activity of a mixture of the two compounds was much higher than that of the sum of the two compounds, suggesting that the two compounds may act synergistically to inhibit the growth of cress and barnyardgrass. The present research suggests that 3-hydroxy-β -ionone and 9-hydroxy-4-megastigmen-3-one may be responsible for the growth inhibitory effect of cv. Kartikshail and may play important roles in the allelopathy of cv. Kartikshail. The traditional Bangladeshi rice cultivar Kartikshail may be potentially useful for weed management as a weed suppressing agent when this rice cultivar is incorporated into the soil or included in rice-based cropping systems.</p>

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Allelopathic potential and chemical composition of rhinacanthus nasutus extracts

Piyatida Pukclai, Suenaga Kiyotake, Kato-Noguchi Hisashi

Allelopathy Journal 26 （ 2 ） 207 - 216 2010年10月

査読有り,  ISSN  0971-4693

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<p>Aqueous methanol extracts of Rhinacanthus nasutus (L.) Kurz inhibited the shoot and root growth of cress (Lepidum sativum L.), lettuce (Lactuca sativa L.), alfalfa (Medicago sativa L.), timothy (Phleum pratense L.), Italian ryegrass (Lolium multiflorum Lam) and crabgrass (Digitaria sanguinalis L.) at concentrations &gt; 0.1 g dry weight equivalent extract/mL and the inhibition increased with increasing extract concentration. These results suggest that the extract of R. nasutus may possess allelopathic activity. An active substance was then isolated and determined by ¹H-, ¹³C-NMR and MS as 4-hydroxy-3-methoxybenzoic acid (vanillic acid). This is the first report of finding the vanillic acid in R. nasutus. The concentrations required for 50% growth inhibition of cress and lettuce were about 470 - 800 μM and the concentrations required for 50% growth inhibition of timothy and Italian ryegrass were 0.17 - 8.2 μM, which suggest that effectiveness of vanillic acid on timothy and Italian ryegrass was much greater than on cress and lettuce. The inhibitory activity and the occurrence of vanillic acid in R. nasutus suggest that vanillic acid may play an important role in the allelopathic properties of R. nasutus. The information obtained could be utilized in the development of bioherbicide for future weed management.</p>

Total synthesis of auripyrones A and B and determination of the absolute configuration of auripyrone B

Hayakawa Ichiro, Takemura Takuma, Fukasawa Emi, Ebihara Yuta, Sato Natsuki, Nakamura Takayasu, Suenaga Kiyotake, Kigoshi Hideo

Angewandte Chemie - International Edition 49 （ 13 ） 2401 - 2405 2010年03月

査読有り,  ISSN  1433-7851

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<p>(Figure Presented) The winner takes it aldol: The total synthesis of auripyrones A and B was achieved using a diastereoselective aldol-type reaction with 2, 6-diethyl-3, 5-dimethyl-4-pyrone as a key step. The stereostructure and absolute configura-tion of auripyrone B has also been determined.</p>

Isolation and identification of potent allelopathic substances in rattail fescue

Kato-Noguchi Hisashi, Yamamoto Madoka, Tamura Kazuya, Teruya Toshiaki, Suenaga Kiyotake, Fujii Yoshiharu

Plant Growth Regulation 60 （ 2 ） 127 - 131 2010年03月

査読有り,  ISSN  0167-6903

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<p>Aqueous methanol extracts of rattail fescue (Vulpia myuros) inhibited the growth of roots and shoots of cress (Lepidium sativum), lettuce (Lactuca sativa), alfalfa (Medicago sativa), timothy (Phleum pratense), Digitaria sanguinalis and Lolium multiflorum. Increasing the extract concentration increased the inhibition, suggesting that rattail fescue may have growth inhibitory substances and possess allelopathic potential. The aqueous methanol extract of rattail fescue was purified and two main inhibitory substances were isolated and identified by spectral data as (-)-3-hydroxy-β-ionone and (+)-3-oxo-α-ionol. Both substances inhibited root and shoot growth of cress at concentrations greater than 0.3 μM. The concentrations required for 50% growth inhibition on root and shoot growth of cress, lettuce, alfalfa, timothy, D. sanguinalis and L. multiflorum were 2.7-19.7 μM for (-)-3-hydroxy-β-ionone, and 2.1-34.5 μM for (+)-3-oxo-α-ionol. The concentration of (-)-3-hydroxy-β-ionone and (+)-3-oxo-α-ionol, respectively, in rattail fescue was 7.8 and 3.7 μg g^-1 fresh weight. Considering the endogenous level and the inhibitory activity, (-)-3-hydroxy-β-ionone and (+)-3-oxo-α-ionol may work as allelopathic substances in rattail fescue through the growth inhibition of neighboring plant species.</p>

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Cytotoxic substances from two species of Japanese sea hares

Yamada Kiyoyuki, Ojika Makoto, Kigoshi Hideo, Suenaga Kiyotake

Proceedings of the Japan Academy Series B: Physical and Biological Sciences 86 （ 3 ） 176 - 189 2010年03月

査読有り,  ISSN  0386-2208

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<p>From the sea hares belonging to two genera, Aplysia and Dolabella, a variety of new cytotoxic substances were isolated as minute constituents: their chemical structures were determined and their cytotoxicity was evaluated. Regarding the highly cytotoxic substances, further chemical and biological studies were performed that included their asymmetric chemical synthesis and elucidation of biological characteristics such as antitumor activity.</p>

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Isolation and structure of koshikalide, a 14-membered macrolide from the marine cyanobacterium Lyngbya sp.

Iwasaki Arihiro, Teruya Toshiaki, Suenaga Kiyotake

Tetrahedron Letters 51 （ 6 ） 959 - 960 2010年02月

査読有り,  ISSN  0040-4039

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<p>A 14-membered macrolide, koshikalide (1), was isolated from the marine cyanobacterium Lyngbya sp., and its planar structure was elucidated by spectroscopic analysis. The relative stereochemistry of C-11 and C-13 was elucidated by NOESY experiments and by an analysis of ¹H-¹H coupling constants. Koshikalide (1) exhibited weak cytotoxicity against HeLa S₃ cells.</p>

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Synthesis of palau'amide and its diastereomers: Confirmation of its stereostructure

Sugiyama Hirokazu, Watanabe Atsushi, Teruya Toshiaki, Suenaga Kiyotake

Tetrahedron Letters 50 （ 52 ） 7343 - 7345 2009年12月

査読有り,  ISSN  0040-4039

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<p>Four diastereomers of palau'amide (1-4), a cytotoxic cyclodepsipeptide, were synthesized. The ¹H NMR spectrum of 1 was identical to that of natural palau'amide. This established the complete stereostructure of palau'amide.</p>

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Isolation of C ₁₁ cyclopentenones from two didemnid species, Lissoclinum sp. and Diplosoma sp.

Ogi Takayuki, Margiastuti Palupi, Teruya Toshiaki, Taira Junsei, Suenaga Kiyotake, Ueda Katsuhiro

Marine Drugs 7 （ 4 ） 816 - 832 2009年12月

査読有り,  ISSN  1660-3397

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<p>A series of new C ₁₁ cyclopentenones 1-7 was isolated, together with four known metabolites 9/10, 12 and 13, from the extract of the didemnid ascidian Lissoclinum sp. The other didemnid ascidian Diplosoma sp. contained didemnenones 1, 2 and 5, and five known metabolites 8-12. The structures of 1-7 were elucidated by spectroscopic analyses. Cytotoxicity of the isolated compounds was evaluated against three human cancer cell lines (HCT116, A431 and A549).</p>

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Bisebromoamide, a potent cytotoxic peptide from the marine cyanobacterium lyngbya sp.

Teruya Toshiaki, Sasaki Hiroaki, Fukazawa Hidesuke, Suenaga Kiyotake

Organic Letters 11 （ 21 ） 5062 - 5065 2009年11月

査読有り,  ISSN  1523-7060

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<p>A novel cytotoxic peptide, termed bisebromoamide (1), has been Isolated from the marine cyanobacterium Lyngbya sp. Its planar structure was determined by 1D and 2D NMR spectroscopy. The absolute stereostructure of 1 was determined by chemical degradation followed by chiral HPLC analysis. Bisebromoamide (1) exhibited potent protein kinase Inhibition: the phosphorylation of ERK In NRK cells by PDGFstimulation was selectively Inhibited by treatment with 10-0.1 μM of 1.</p>

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Unusual intramolecular N→O acyl group migration occurring during conjugation of (-)-DHMEQ with cysteine

Kozawa Ikuko, Kato Kuniki, Teruya Toshiaki, Suenaga Kiyotake, Umezawa Kazuo

Bioorganic and Medicinal Chemistry Letters 19 （ 18 ） 5380 - 5382 2009年09月

査読有り,  ISSN  0960-894X

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<p>Previously we found that (-)-DHMEQ, a specific NF-κB inhibitor, covalently bound to a specific cysteine of NF-κB component proteins. In the course of formation of the (-)-DHMEQ and protected cysteine conjugate, we observed an unusual intramolecular N→O acyl group migration.</p>

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Synthetic studies on reidispongiolide A, an actin-depolymerizing marine macrolide: Synthesis of C11-C22 and C23-C35 segments.

Akiyama Satoshi, Toriihara Eisuke, Suzuki Kazushi, Teruya Toshiaki, Suenaga Kiyotake

Tetrahedron Letters 50 （ 35 ） 5012 - 5014 2009年09月

査読有り,  ISSN  0040-4039

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<p>The C11-C22 and C23-C35 segments 2 and 3 of reidispongiolide A (1), an actin-depolymerizing marine macrolide, were synthesized enantioselectively in 12 steps from (R)-glycidyl trityl ether and in 12 steps from chiral ketone 15, respectively.</p>

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Biselyngbyaside, a macrolide glycoside from the marine cyanobacterium lyngbya sp.

Teruya Toshiaki, Sasaki Hiroaki, Kitamura Kazuhiro, Nakayama Takeshi, Suenaga Kiyotake

Organic Letters 11 （ 11 ） 2421 - 2424 2009年06月

査読有り,  ISSN  1523-7060

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<p>Bioassay-guided fractionation of the cytotoxic constituents of the marine cyanobacterium Lyngbya sp. led to the isolation of biselyngbyaside (1), a new 18-membered macrolide glycoside. The structure of 1 was established by spectroscopic analysis including 2D-NMR techniques and by synthetic studies. Biselyngbyaside (1) exhibits broad-spectrum cytotoxicity in a human tumor cell line panel.</p>

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Isolation and identification of a potent allelopathic substance in Bangladesh rice

Salam Md Abdus, Morokuma Masahiro, Teruya Toshiaki, Suenaga Kiyotake, Kato-Noguchi Hisashi

Plant Growth Regulation 58 （ 2 ） 137 - 140 2009年06月

査読有り,  ISSN  0167-6903

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<p>Aqueous methanol extracts of Bangladesh rice (Oryza sativa L. cv. BR17) inhibited the growth of roots and shoots of cress (Lepidium sativum), lettuce (Lactuca sativa), alfalfa (Medicago sativa), timothy (Phleum pratense), Digitaria sanguinalis, Echinochloa crus-galli and Echinochloa colonum. Increasing the extract concentration increased the inhibition, suggesting that the BR17 may have growth inhibitory substances and possess allelopathic potential. The aqueous methanol extract of the BR17 was purified and a main inhibitory substance was isolated and determined by spectral data as 2,9-dihydroxy-4-megastigmen-3-one. This substance inhibited root and shoot growth of cress and E. crus-galli seedlings at concentrations greater than 0.03 and 3 μM, respectively. The concentrations required for 50% growth inhibition on cress roots and shoots were 0.22 and 0.47 μM, respectively, and on E. crus-galli roots and shoots were 36 and 133 μM, respectively. These results suggest that 2,9-dihydroxy-4-megastigmen-3-one may contribute to the growth inhibitory effect of BR17 and may play an important role in the allelopathy of BR17. Thus, Bangladesh rice BR17 may be potentially useful for weed management in a field setting.</p>

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Synthesis of actin-depolymerizing compounds

Kitamura Kazuhiro, Teruya Toshiaki, Kuroda Takeshi, Kigoshi Hideo, Suenaga Kiyotake

Bioorganic and Medicinal Chemistry Letters 19 （ 7 ） 1896 - 1898 2009年04月

査読有り,  ISSN  0960-894X

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<p>The artificial actin-depolymerizing compounds 3-6, based on aplyronine A, an actin-depolymerizing antitumor marine macrolide, were synthesized, and their actin-depolymerizing activities and cytotoxicities were evaluated.</p>

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Synthetic studies of mangostin derivatives with an inhibitory activity on PDGF-induced human aortic smooth cells proliferation

Nishihama Yuko, Ogamino Takahisa, Shi Wen Lei, Cha Byung Yoon, Yonezawa Takayuki, Teruya Toshiaki, Nagai Kazuo, Suenaga Kiyotake, Woo Je Tae, Nishiyama Shigeru

Heterocycles 77 （ 2 ） 759 - 765 2009年02月

査読有り,  ISSN  0385-5414

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<p>The mangostin derivatives 310, were synthesized by halogenation, electrochemical oxidation, and mCPBA oxidation of α- and γ-mangostins (1, 2). Among them, the hydroxyl 9 and the benzopyran 10 derivatives produced by mCPBA, showed remarkable antiproliferative activities against human aortic smooth muscle cells (HASMC) induced by platelet-derived growth factor (PDGF).</p>

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Erratum to Isolation and identification of a potent allelopathic substance in Bangladesh rice (Plant Growth Regul, (2009), 58, (137-140), 10.1007/s10725-009-9360-5)

Salam Md Abdus, Morokuma Masahiro, Teruya Toshiaki, Suenaga Kiyotake, Kato-Noguchi Hisashi

Plant Growth Regulation 59 （ 2 ） 189 2009年

査読有り,  ISSN  0167-6903

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