論文 - 末永　聖武

An inhibitor of the adipogenic differentiation of 3T3-L1 cells, yoshinone A, and its analogs, isolated from the marine cyanobacterium Leptolyngbya sp.

Inuzuka Toshiyasu, Yamamoto Keita, Iwasaki Arihiro, Ohno Osamu, Suenaga Kiyotake, Kawazoe Yoshinori, Uemura Daisuke

Tetrahedron Letters 55 （ 49 ） 6711 - 6714 2014年12月

査読有り,  ISSN  0040-4039

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<p>Three novel compounds, yoshinones A, B1, and B2, were isolated from the marine cyanobacterium Leptolyngbya sp., and their structures were elucidated by NMR spectral analysis. Yoshinone A, but not yoshinone B1 or B2, inhibited the differentiation of 3T3-L1 cells into adipocytes. In addition, yoshinone A did not exhibit cytotoxicity, suggesting that yoshinone A may be useful in studies on the treatment of obesity.</p>

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Suaveolic Acid: A Potent Phytotoxic Substance of Hyptis suaveolens.

Islam A. K M Mominul, Ohno Osamu, Suenaga Kiyotake, Kato-Noguchi Hisashi

Scientific World Journal 2014   Article ID 425942 (6 pages) 2014年10月

査読有り,  ISSN  2356-6140

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<p>Hyptis suaveolens (Lamiaceae) is an exotic invasive plant in many countries. Earlier studies reported that the aqueous, methanol, and aqueous methanol extract of H. suaveolens and its residues have phytotoxic properties. However, to date, the phytotoxic substances of this plant have not been reported. Therefore, the objectives of this study were isolation and identification of phytotoxic substances of H. suaveolens. Aqueous methanol extract of this plant was purified by several chromatographic runs through bioassay guided fractionation using garden cress (Lepidium sativum) as a test plant. Final purification of a phytotoxic substance was achieved by reverse phase HPLC and characterized as 14α-hydroxy-13β-abiet-8-en-18-oic acid (suaveolic acid) by high-resolution ESI-MS, ¹H-,¹³C-NMR, CD, and specific rotation. Suaveolic acid inhibited the shoot growth of garden cress, lettuce (Lactuca sativa), Italian ryegrass (Lolium multiflorum), and barnyard grass (Echinochloa crus-galli) at concentrations greater than 30 μM. Root growth of all but lettuce was also inhibited at concentrations greater than 30 μM. The inhibitory activities were concentration dependent. Concentrations required for 50% growth inhibition of suaveolic acid for those test plant species were ranged from 76 to 1155 μM. Therefore, suaveolic acid is phytotoxic and may be responsible for the phytotoxicity of H. suaveolens plant extracts.</p>

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Maedamide, a novel chymotrypsin inhibitor from a marine cyanobacterial assemblage of Lyngbya sp.

Iwasaki Arihiro, Ohno Osamu, Sumimoto Shinpei, Suda Shoichiro, Suenaga Kiyotake

Tetrahedron Letters 55 （ 30 ） 4126 - 4128 2014年07月

査読有り,  ISSN  0040-4039

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<p>Maedamide, a novel chymotrypsin-inhibiting depsipeptide, was isolated from a cyanobacterial assemblage that mostly consisted of Lyngbya sp. Its structure was elucidated by spectroscopic analyses and chiral HPLC analyses of hydrolysis products. Maedamide selectively inhibited chymotrypsin but not elastase and trypsin. In addition, Maedamide strongly inhibited the growth of HeLa cells and HL60 cells.</p>

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Two novel phytotoxic substances from Leucas aspera

Islam A. K M Mominul, Ohno Osamu, Suenaga Kiyotake, Kato-Noguchi Hisashi

Journal of Plant Physiology 171 （ 11 ） 877 - 883 2014年07月

査読有り,  ISSN  0176-1617

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<p>Leucas aspera (Lamiaceae), an aromatic herbaceous plant, is well known for many medicinal properties and a number of bioactive compounds against animal cells have been isolated. However, phytotoxic substances from L. aspera have not yet been documented in the literature. Therefore, current research was conducted to explore the phytotoxic properties and substances in L. aspera. Aqueous methanol extracts of L. aspera inhibited the germination and growth of garden cress (Lepidum sativum) and barnyard grass (Echinochloa crus-galli), and the inhibitory activities were concentration dependent. These results suggest that the plant may have phytotoxic substances. The extracts were then purified by several chromatographic runs. The final purification was achieved by reversed-phase HPLC to give an equilibrium (or inseparable) 3:2 mixture of two labdane type diterpenes (compounds 1 and 2). These compounds were characterized as (rel 5S,6R,8R,9R,10S,13S,15S,16R)-6-acetoxy-9,13;15,16-diepoxy-15-hydroxy-16-methoxylabdane (1) and (rel 5S,6R,8R,9R,10S,13S,15R,16R)-6-acetoxy-9,13;15,16-diepoxy-15-hydroxy-16-methoxylabdane (2) by spectroscopic analyses. A mixture of the two compounds inhibits the germination and seedling growth of garden cress and barnyard grass at concentrations greater than 30 and 3μM, respectively. The concentration required for 50% growth inhibition (I₅₀) of the test species ranges from 31 to 80μM, which suggests that the mixture of these compounds, are responsible for the phytotoxic activity of L. aspera plant extract.</p>

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Growth limiting effects on various terrestrial plant species by an allelopathic substance, loliolide, from water hyacinth

Kato-Noguchi, Hisashi, Moriyasu, Mayumi, Ohno, Osamu, Suenaga, Kiyotake

AQUATIC BOTANY 117   56 - 61 2014年07月

研究論文（学術雑誌）, 査読有り,  ISSN  0304-3770

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Isolation and identification of a plant growth inhibitor from Tinospora tuberculata Beumee

Kato-Noguchi Hisashi, Pukclai Piyatida, Ohno Osamu, Suenaga Kiyotake

Acta Physiologiae Plantarum 36 （ 7 ） 1621 - 1626 2014年07月

査読有り,  ISSN  0137-5881

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<p>Tinospora tuberculata Beumee has been used widely as a folk medicine and several bioactive compounds have been isolated. However, no herbicidal compound has been reported in this species. Therefore, we investigated the presence of phytotoxins in T. tuberculata. The aqueous methanol extracts of T. tuberculata inhibited the growth of roots and shoots of cress (Lepidum sativum L.), lettuce (Lactuca sativa L.), timothy (Phleum pratense L.) and barnyard grass (Echinochloa crus-galli (L.) Beauv.). The extract was then purified by several chromatographic runs with monitoring the inhibitory activity and the main phytotoxic substance was isolated. The chemical structure of the compound was determined by spectral data as syringin (4-[(1E)-3-Hydroxyprop-1-en-1-yl]-2,6-dimethoxyphenyl β-d-glucopyranoside). It inhibited the root and shoot growth of all test plant species at concentrations &gt;10 μM. The concentrations required for 50 % inhibition of root and shoot growth of cress and lettuce ranged from 78.2 to 412 μM, and that of timothy and barnyard grass renged from 9.8 to 73.2 μM. Effectiveness of syringin on monocotyledonous (timothy and barnyard grass) plants was greater than that on dicotyledonous (cress and lettuce) plants. These results suggest that syringin may contribute to the allelopathic effect caused by the T. tuberculata extract.</p>

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Total synthesis of biselyngbyolide A

Tanabe Yurika, Sato Eisuke, Nakajima Naoya, Ohkubo Akifumi, Ohno Osamu, Suenaga Kiyotake

Organic Letters 16 （ 11 ） 2858 - 2861 2014年06月

査読有り,  ISSN  1523-7060

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<p>Biselyngbyolide A is an 18-membered macrolide that exhibits significant biological activities such as growth-inhibitory activity and apoptosis inducing activity against cancer cells. In this study, the first total synthesis of biselyngbyolide A by using an intramolecular Stille coupling reaction as a key step is achieved.</p>

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Nimbolide B and Nimbic Acid B, Phytotoxic Substances in Neem Leaves with Allelopathic Activity

Kato-Noguchi, Hisashi, Salam, Md Abdus, Ohno, Osamu, Suenaga, Kiyotake

MOLECULES 19 （ 6 ） 6929 - 6940 2014年06月

研究論文（学術雑誌）, 査読有り,  ISSN  1420-3049

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Kurahamide, a cyclic depsipeptide analog of dolastatin 13 from a marine cyanobacterial assemblage of Lyngbya sp.

Iwasaki Arihiro, Sumimoto Shinpei, Ohno Osamu, Suda Shoichiro, Suenaga Kiyotake

Bulletin of the Chemical Society of Japan 87 （ 5 ） 609 - 613 2014年05月

査読有り,  ISSN  0009-2673

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<p>Kurahamide, a new dolastatin 13 analog, was isolated from a marine cyanobacterial assemblage, consisting mostly of Lyngbya sp. Its gross structure was elucidated by spectroscopic analysis, and the stereochemistries were assigned based on a chiral HPLC analysis of hydrolysis products. Kurahamide strongly inhibited elastase and chymotrypsin in vitro. In addition, kurahamide moderately inhibited the growth of human cancer cells, including HeLa and HL60 cells.</p>

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Phytotoxic substances with allelopathic activity may be central to the strong invasive potential of Brachiaria brizantha

Kato-Noguchi Hisashi, Kobayashi Ai, Ohno Osamu, Kimura Fukiko, Fujii Yoshiharu, Suenaga Kiyotake

Journal of Plant Physiology 171 （ 7 ） 525 - 530 2014年04月

査読有り,  ISSN  0176-1617

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<p>The grass Brachiaria brizantha, native to eastern Africa, becomes naturalized and dominant quickly in the non-native areas. It was hypothesized that phytotoxic chemical interaction between this plant and native plants may play an important role in the invasion of B. brizantha. However, no potent phytotoxic substance has been reported in this species. Therefore, we investigated possible allelopathic activity and searched for phytotoxic substances with allelopathic activity in B. brizantha. An aqueous methanol extract of B. brizantha inhibited the growth of roots and shoots of garden cress (Lepidium sativum), lettuce (Lactuca sativa), timothy (Phleum pratense) and ryegrass (Lolium multiflorum) seedlings. The extract was purified by several chromatographic runs and three allelopathically active substances were isolated and identified by spectral analysis as (6R,. 9R)-3-oxo-α-ionol, (6R,. 9S)-3-oxo-α-ionol and 4-ketopinoresinol. (6R,. 9R)-3-Oxo-α-ionol and (6R,. 9S)-3-oxo-α-ionol inhibited root and shoot growth of garden cress at concentrations greater than 30 and 10. μM, respectively. The activity of (6R,. 9S)-3-oxo-α-ionol was 5.3- to 6.2-fold that of (6R,. 9R)-3-oxo-α-ionol. The stereochemistry of the hydroxyl group at position C-9 may be important for the inhibitory activities of those compounds. 4-Ketopinoresinol inhibited root and shoot growth of garden cress at concentrations greater than 30. μM. The growth inhibitory activity of (6R,. 9S)-3-oxo-α-ionol was the greatest and followed by 4-ketopinoresinol and (6R,. 9R)-3-oxo-α-ionol. These results suggest that those phytotoxic substances may contribute to the allelopathic effect caused by B. brizantha and may be involved in the invasion of B. brizantha.</p>

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Biselyngbyolide B, a Novel ER Stress-inducer Isolated from the Marine Cyanobacterium Lyngbya sp.

Osamu Ohno, Ayane Watanabe, Maho Morita, and Kiyotake Suenaga

Chemistry Letters 43 （ 3 ） 287-289 2014年03月

研究論文（学術雑誌）, 査読有り

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Kurahyne, an acetylene-containing lipopeptide from a marine cyanobacterial assemblage of Lyngbya sp.

Arihiro Iwasaki, Osamu Ohno, Shinpei Sumimoto, Shoichiro Suda, and Kiyotake Suenaga

RSC Advances 4   12840-12843 2014年02月

研究論文（学術雑誌）, 共著, 査読有り

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A novel substance with allelopathic activity in Ginkgo biloba

Kato-Noguchi Hisashi, Takeshita Sayaka, Kimura Fukiko, Ohno Osamu, Suenaga Kiyotake

Journal of Plant Physiology 170 （ 18 ） 1595 - 1599 2013年12月

査読有り,  ISSN  0176-1617

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<p>Ginkgo (Ginkgo biloba) is one of the oldest living tree species and has been widely used in traditional medicine. Leaf extracts of ginkgo, such as the standardized extract EGb761, have become one of the best-selling herbal products. However, no bioactive compound directed at plants has been reported in this species. Therefore, we investigated possible allelopathic activity and searched for allelopathically active substances in ginkgo leaves. An aqueous methanol leaf extract inhibited the growth of roots and shoots of garden cress (Lepidium sativum), lettuce (Lactuca sativa), timothy (Phleum pratense) and ryegrass (Lolium multiflorum) seedlings. The extract was purified by several chromatographic runs and an allelopathically active substance was isolated and identified by spectral analysis to be the novel compound 2-hydroxy-6-(10-hydroxypentadec-11-enyl)benzoic acid. The compound inhibited root and shoot growth of garden cress and timothy at concentrations greater than 3. μM. The activity of the compound was 10- to 52-fold that of nonanoic acid. These results suggest that 2-hydroxy-6-(10-hydroxypentadec-11-enyl)benzoic acid may contribute to the allelopathic effect caused by ginkgo leaf extract. The compound may also have potential as a template for the development of new plant control substances.</p>

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Isolation and identification of an allelopathic substance from duckweed (Lemna minor L.)

Tran Thi Ngoc Bich, Osamu Ohno, Kiyotake Suenaga, and Hisashi Kato-Noguchi

Allelopathy Journal 32 （ 2 ） 213 - 222 2013年10月

研究論文（学術雑誌）, 共著, 査読有り

Effects of the methoxy group in the side chain of debromoaplysiatoxin on its tumor-promoting and anti-proliferative activities

Yanagita Ryo C., Kamachi Hiroaki, Kikumori Masayuki, Tokuda Harukuni, Suzuki Nobutaka, Suenaga Kiyotake, Nagai Hiroshi, Irie Kazuhiro

Bioorganic and Medicinal Chemistry Letters 23 （ 15 ） 4319 - 4323 2013年08月

査読有り,  ISSN  0960-894X

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<p>Debromoaplysiatoxin (DAT) is a tumor promoter isolated from sea hare and exhibits anti-proliferative activity against several cancer cell lines. To clarify key residues that are responsible for its tumor-promoting activity, we focused on the chiral methoxy group in the side chain, whose role had not yet been discussed or examined before. Demethoxy-DAT (8) was derived from DAT and we evaluated its tumor-promoting activity, anti-proliferative activity, and ability to bind to protein kinase C (PKC) isozymes. Compound 8 showed somewhat weaker tumor-promoting activity than that of DAT both in vitro and in vivo, but showed higher anti-proliferative activity against several cancer cell lines. Although the affinity to novel PKC isozymes of 8 was comparable to that of DAT, the affinity to conventional PKC isozymes decreased slightly. These results suggest that the methoxy group of DAT is one of the key residues critical for tumor-promoting activity but not for anti-proliferative activity. Since the methoxy group has little influence on the molecular hydrophobicity, this is the first report showing that structural factors other than hydrophobicity in the side chain of DAT affected its biological activities.</p>

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Allelopathy is involved in the formation of pure colonies of the fern Gleichenia japonica

Kato-Noguchi Hisashi, Saito Yoshihumi, Ohno Osamu, Suenaga Kiyotake

Journal of Plant Physiology 170 （ 6 ） 577 - 582 2013年04月

査読有り,  ISSN  0176-1617

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<p>The fern Gleichenia japonica is one of the most widely distributed fern and occurs throughout East to South Asia. The species often dominates plant communities by forming large monospecific colonies. However, the potential mechanism for this domination has not yet been described. The objective of this study was to test the hypothesis that allelochemicals are involved in the formation of G. japonica colonies. An aqueous methanol extract of G. japonica inhibited the growth of seedlings of garden cress (Lepidium sativum), lettuce (Lactuca sativa), ryegrass (Lolium multiflorum) and timothy (Phleum pratense). Increasing extract concentration increased the inhibition. These results suggest that G. japonica contain allelopathic substances. The extract was then purified by several chromatographies with monitoring the inhibitory activity and two growth inhibitory substances causing the allelopathic effect were isolated. The chemical structures of the two substances were determined by spectral data to be a novel compound 3- O-β-allopyranosyl-13- O-β-fucopyranosyl-3β-hydroxymanool (1) and 18- O-α- l-rhamnopyranosyl-(1→2)-β- d-glucopyranosyl-13-epitorreferol (2). These compounds inhibited the shoot and root growth of garden cress, lettuce, alfalfa (Medicago sativa), timothy, ryegrass and barnyardgrass (Echinochloa crus-galli) at concentrations greater than 0.1-1.0 mM. The concentrations required for 50% growth inhibition of root and shoot growth of these test plants ranged from 0.72 to 3.49 mM and 0.79 to 3.51 mM for compounds 1 and 2, respectively. Concentration of compounds 1 and 2 in soil under the pure colony of G. japonica was 4.9 and 5.7 mM, respectively, indicating concentrations over those required for 50% growth inhibition are potentially available under monocultural stands of these ferns. Therefore, these compounds may contribute to the allelopathic effects caused by presence of G. japonica and may thus contribute to the establishment of monocultural stands by this fern.</p>

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Total synthesis, structural elucidation, and structure-cytotoxic activity relationship of (-)-gummiferol

Takamura Hiroyoshi, Wada Hiroko, Lu Nan, Ohno Osamu, Suenaga Kiyotake, Kadota Isao

Journal of Organic Chemistry 78 （ 6 ） 2443 - 2454 2013年03月

査読有り,  ISSN  0022-3263

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<p>A highly stereoselective and stereodivergent synthesis of two possible diastereomers of (-)-gummiferol was achieved, wherein the stepwise epoxidation and Cadiot-Chodkiewicz reaction were utilized for the construction of the diepoxide moiety and triacetylene part, respectively. Detailed comparison of their ¹H and ¹³C NMR data and specific rotation with those of the natural product unambiguously elucidated the absolute stereostructure of gummiferol. In addition, the cytotoxic activity of the synthesized gummiferol, its stereoisomers, and its truncated analogues was evaluated, which clearly indicates that (1) the absolute configuration of the diepoxide moiety has little influence on the cytotoxic activity against human cancer cells and (2) the triacetylene unit is the crucial structural element required for exerting the cytotoxic activity.</p>

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Apoptosis-inducing activity of the actin-depolymerizing agent aplyronine A and its side-chain derivatives

Ohno Osamu, Morita Maho, Kitamura Kazuhiro, Teruya Toshiaki, Yoneda Kozo, Kita Masaki, Kigoshi Hideo, Suenaga Kiyotake

Bioorganic and Medicinal Chemistry Letters 23 （ 5 ） 1467 - 1471 2013年03月

査読有り,  ISSN  0960-894X

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<p>Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S₃ cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity.</p>

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A novel allelopathic substance, 13-epi-orthosiphol N, in Orthosiphon stamineus

Kato-Noguchi Hisashi, Hamada Naoko, Morita Maho, Suenaga Kiyotake

Journal of Plant Physiology 170 （ 1 ） 1 - 5 2013年01月

査読有り,  ISSN  0176-1617

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<p>Orthosiphon stamineus (Java tea) has been widely used as traditional herb and several bioactive compounds against animal cells have been isolated. However, no bioactive compound against plants has been reported. Therefore, we investigated possible allelopathic properties and substances in O. stamineus. Aqueous methanol extracts of O. stamineus inhibited root and hypocotyl growth of cress (Lepidium sativum) and lettuce (Lactuca sativa) seedlings. Increasing the extract concentration increased the inhibition, which suggests that O. stamineus may have allelopathic properties. When the extract was divided into an ethyl acetate and an aqueous fraction, the ethyl acetate fraction showed the stronger inhibitory effect. Thus, the ethyl acetate phase was further purified, and the main allelopathic substance was isolated and identified as 13- epi-orthosiphol N, a novel compound, by spectral data. 13- epi-Orthosiphol N inhibited root and hypocotyl growth of cress and lettuce at concentrations greater than 10 μmol/L. The concentrations required for 50% inhibition ranged from 41 to 102 μmol/L. These results suggest that 13- epi-orthosiphol N may be an allelochemical and main contributor to the growth inhibitory effect of O. stamineus and may have potential as a template for the development of new plant control substances.</p>

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Bisebromoamide, an extract from Lyngbya species, induces apoptosis through ERK and mTOR inhibitions in renal cancer cells.

Kenjiro Suzuki, Ryuichi Mizuno, Kiyotake Suenaga, Toshiaki Teruya, Nobuyuki Tanaka, Takeo Kosaka, Mototsugu Oya:

Cancer Medicine 2 （ 1 ） 32-39 2013年

研究論文（学術雑誌）, 共著, 査読有り