Papers - Suenaga, Kiyotake

Immunological Adjuvant Activity of Pectinioside A, the Steroidal Saponin from the Starfish Patiria pectinifera

Kawase Osamu, Ohno Osamu, Suenaga Kiyotake, Xuan Xuenan

Natural Product Communications 11 ( 5 ) 605 - 606 2016.05

Accepted,  ISSN  1934-578X

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<p>The steroidal saponin, pectinioside A, was isolated from the starfish, Patiria pectinifera. When it was subcutaneously injected into mice with ovalbumin (OVA), it facilitated the production of OVA-specific total IgG and IgG1 but not IgG2a. To our knowledge, this is the first report suggesting that starfish saponin has the potential to be an immunological adjuvant, stimulating Th2 type immune response.</p>

A Potent Phytotoxic Substance in Aglaia odorata Lour.

Kato-Noguchi Hisashi, Suzuki Masahiko, Noguchi Kazutaka, Ohno Osamu, Suenaga Kiyotake, Laosinwattana Chamroon

Chemistry and Biodiversity 13 ( 5 ) 549 - 554 2016.05

Accepted,  ISSN  1612-1872

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<p>Aglaia odorata Lour. (Meliaceae) was found to have very strong allelopathic activity and a bioherbicide PORGANIC^™ was developed from its leaf extracts. However, the phytotoxic substances causing the strong allelopathic activity of the plants have not yet been determined. Therefore, we investigated allelopathic properties and phytotoxic substances in A. odorata. Aqueous EtOH extracts of A. odorata leaves inhibited root and shoot growth of garden cress (Lepidum sativum), lettuce (Lactuca sativa), alfalfa (Medicago sativa), timothy (Phleum pratense), ryegrass (Lolium multiflorum), and Echinochloa crus-galli with the extract concentration-dependent manner. The extracts were then purified and a major phytotoxic substance with allelopathic activity was isolated and identified by spectral data as rocaglaol. Rocaglaol inhibited the growth of garden cress and E. crus-galli at concentrations &gt; 0.3 and 0.03 μm, respectively. The concentrations required for 50% inhibition ranged from 0.09 to 2.5 μm. The inhibitory activity of rocaglaol on the weed species, E. crus-galli, was much greater than that of abscisic acid. These results suggest that rocaglaol may be a major contributor to the allelopathic effect of A. odorata and bioherbicide PORGANIC^™.</p>

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Anti-obesity activities of the yoshinone A and the related marine γ-pyrone compounds

Koyama Tomoyuki, Kawazoe Yoshinori, Iwasaki Arihiro, Ohno Osamu, Suenaga Kiyotake, Uemura Daisuke

Journal of Antibiotics 69 ( 4 ) 348 - 351 2016.04

Accepted,  ISSN  0021-8820

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Structural optimization of 10-methyl-aplog-1, a simplified analog of debromoaplysiatoxin, as an anticancer lead

Kikumori Masayuki, Yanagita Ryo C., Tokuda Harukuni, Suenaga Kiyotake, Nagai Hiroshi, Irie Kazuhiro

Bioscience, Biotechnology and Biochemistry 80 ( 2 ) 221 - 231 2016.02

Accepted,  ISSN  0916-8451

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<p>Aplog-1 is a simplified analog of debromoaplysiatoxin (DAT) with potent tumor-promoting and proinflammatory activities. Aplog-1 and DAT exhibited anti-proliferative activities against several human cancer cell lines, whereas aplog-1 did not have tumor-promoting nor proinflammatory activities. We have recently found 10-methyl-aplog-1 (1) to have strong anti-proliferative activity compared with aplog-1. To further investigate the structural factors involved in the tumor-promoting, proinflammatory, and anti-proliferative activities, two dimethyl derivatives of aplog-1 (2, 3) were synthesized, where two methyl groups were installed at positions 4 and 10 or 10 and 12. 10,12-Dimethyl-aplog-1 (2) had stronger inhibitory effects on the growth of several human cancer cell lines than 1 and DAT, but exhibited no tumor-promoting and proinflammatory activities. In contrast, 4,10-dimethyl-aplog-1 (3) displayed weak tumor-promoting and proinflammatory activities along with anti-proliferative activity similar to that of 1 and DAT. Compound 2 would be the optimized seed for anticancer drugs among the simplified analogs of DAT.</p>

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Isolation and Structure of Kurahyne B and Total Synthesis of the Kurahynes

Okamoto Shinichiro, Iwasaki Arihiro, Ohno Osamu, Suenaga Kiyotake

Journal of Natural Products 78 ( 11 ) 2719 - 2725 2015.11

Accepted,  ISSN  0163-3864

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<p>Kurahyne B (2), a new analogue of kurahyne (1), was isolated from the marine cyanobacterium Okeania sp. Its gross structure was elucidated based on spectroscopic analyses, and the absolute configuration was established by total synthesis. Kurahyne B (2) inhibited the growth of both HeLa and HL60 cells, with IC₅₀ values of 8.1 and 9.0 μM, respectively. The growth-inhibitory activity of kurahyne B was the same as kurahyne (1). In parallel, the first total synthesis of kurahyne (1) was also achieved.</p>

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Identification of a molecular target of kurahyne, an apoptosis-inducing lipopeptide from marine cyanobacterial assemblages

Iwasaki Arihiro, Ohno Osamu, Katsuyama Shun, Morita Maho, Sasazawa Yukiko, Dan Shingo, Simizu Siro, Yamori Takao, Suenaga Kiyotake

Bioorganic and Medicinal Chemistry Letters 25 ( 22 ) 5295 - 5298 2015.11

Accepted,  ISSN  0960-894X

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<p>In 2014, we isolated kurahyne, an acetylene-containing lipopeptide, from a marine cyanobacterial assemblage of Lyngbya sp. Kurahyne exhibited growth-inhibitory activity against human cancer cells, and induced apoptosis in HeLa cells. However, its mode of action is not yet clear. To elucidate its mode of action, we carried out several cell-based assays, and identified the intracellular target molecule of kurahyne as sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA). In addition, we found that kurahyne inhibited the differentiation of macrophages into osteoclasts.</p>

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Structures and Biological Activities of Novel Biselyngbyaside Analogs Isolated from the Marine Cyanobacterium Lyngbya sp.

Watanabe, Ayane, Ohno, Osamu, Morita, Maho, Inuzuka, Toshiyasu, Suenaga, Kiyotake

BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 88 ( 9 ) 1256 - 1264 2015.09

Research paper (scientific journal),  ISSN  0009-2673

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Synthesis and structure-activity relationships for cytotoxicity and apoptosis-inducing activity of (+)-halichonine B

Hayakawa Ichiro, Nakamura Tomomi, Ohno Osamu, Suenaga Kiyotake, Kigoshi Hideo

Organic and Biomolecular Chemistry 13 ( 39 ) 9969 - 9976 2015.08

Accepted,  ISSN  1477-0520

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<p>Halichonine B is a sesquiterpene alkaloid isolated from the marine sponge Halichondria okadai Kadota. Halichonine B has exhibited cytotoxicity against mammalian cancer cells and induced apoptosis in the human leukemia cell line HL60. Here we established a practical route for the synthesis of halichonine B and its analogues, and we evaluated their biological activities. It was revealed that the secondary amino groups in the side chain portion are important for the strong cytotoxicity of halichonine B and that the N&lt;sup&gt;11&lt;/sup&gt;-prenyl group is unimportant. Halichonine B and its analogues were also observed to induce apoptosis in HL60 cells.</p>

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Isolation of Monovalerianester A, an Inhibitor of Fat Accumulation, from Valeriana fauriei

Yuki Keiji, Ikeda Mariko, Yoshida Shosuke, Ohno Osamu, Suenaga Kiyotake, Yamada Kaoru, Uemura Daisuke, Miyamoto Kenji

Natural Product Communications 10 ( 8 ) 1333 - 1334 2015.08

Accepted,  ISSN  1934-578X

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<p>The rhizomes and roots of Valeriana fauriei were extracted with 80% aqueous ethanol. This extract was found to exhibit potent inhibitory effects on fat accumulation in 3T3-LI murine adipocytes. After several steps of chromatographic purification, we succeeded in identifying monovalerianester A as an inhibitor of fat accumulation. Thus, monovalerianester A and the crude extract of the rhizomes and roots of V. fauriei may have therapeutic potential for the treatment of obesity.</p>

Total synthesis and stereochemical reassignment of maedamide

Takayanagi Ayano, Iwasaki Arihiro, Suenaga Kiyotake

Tetrahedron Letters 56 ( 34 ) 4947 - 4949 2015.05

Accepted,  ISSN  0040-4039

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<p>Abstract The first total synthesis of maedamide, an acyclic peptide isolated from a marine cyanobacterial assemblage of Lyngbya sp., was achieved. This synthesis led to reassignment of the allo-d-Ile of maedamide to be l-Ile, which was supported by &lt;sup&gt;1&lt;/sup&gt;H and &lt;sup&gt;13&lt;/sup&gt;C NMR data.</p>

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Biselyngbyasides, cytotoxic marine macrolides, are novel and potent inhibitors of the Ca²⁺ pumps with a unique mode of binding

Morita Maho, Ogawa Haruo, Ohno Osamu, Yamori Takao, Suenaga Kiyotake, Toyoshima Chikashi

FEBS Letters 589 ( 13 ) 1406 - 1411 2015.05

Accepted,  ISSN  0014-5793

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<p>Biselyngbyasides (BLSs), macrolides from a marine cyanobacterium, are cytotoxic natural products whose target molecule is unknown. Here we report that BLSs are high affinity (K&lt;inf&gt;i&lt;/inf&gt; ∼ 10 nM) inhibitors of Ca&lt;sup&gt;2+&lt;/sup&gt;-pumps with a unique binding mode. The crystal structures of the Ca&lt;sup&gt;2+&lt;/sup&gt;-pump in complex with BLSs at 3.2-3.5 Å-resolution show that BLSs bind to the pump near the cytoplasmic surface of the transmembrane region. The crystal structures and activity measurement of BLS analogs allow us to identify the structural features that confer high potency to BLSs as inhibitors of the pump.</p>

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Isolation and Identification of an Allelopathic Substance from Hibiscus sabdariffa

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

Natural Product Communications 10 ( 5 ) 765 - 770 2015.05

Research paper (scientific journal),  ISSN  1934-578X

Mebamamides A and B, Cyclic Lipopeptides Isolated from the Green Alga Derbesia marina

Iwasaki Arihiro, Ohno Osamu, Sumimoto Shinpei, Matsubara Teruhiko, Shimada Satoshi, Sato Toshinori, Suenaga Kiyotake

Journal of Natural Products 78 ( 4 ) 901 - 908 2015.04

Accepted,  ISSN  0163-3864

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<p>Mebamamides A and B, new lipopeptides with four d-amino acid residues and a 3,8-dihydroxy-9-methyldecanoic acid residue, were isolated from the green alga Derbesia marina. Their gross structures were elucidated by spectroscopic and ESI-ITMS analyses. The absolute configurations except for the two leucines were revealed based on chiral-phase HPLC analyses of the acid hydrolysate and a modified Mosher's method. A distinction between d-Leu and l-Leu in the sequence was established by the application of a dansyl-Edman method to the partial acid hydrolysate. Mebamamide A did not exhibit any growth inhibitory activity against HeLa and HL60 cells at 10 μM, and mebamamide B did not exhibit any growth inhibitory activity against those cells at 100 μM. Additionally, it was suggested that mebamamide B induced the differentiation of HL60 cells into macrophage-like cells at 100 μM. (Chemical Equation).</p>

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A phytotoxic active substance in the decomposing litter of the fern Gleichenia japonica

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

Journal of Plant Physiology 176   55 - 60 2015.03

Accepted,  ISSN  0176-1617

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<p>The fern Gleichenia japonica often dominates plant communities by forming large monospecific stands throughout the temperate to tropical Asia. The objective of this study was the investigation of allelopathic property and substances of the decomposing litter of the fern to evaluate the possible involvement of its allelopathy in the domination. An aqueous methanol extract of G. japonica litter inhibited the growth of garden cress (Lepidium sativum), lettuce (Lactuca sativa), barnyard grass (Echinochloa crus-galli), and ryegrass (Lolium multiflorum). This result suggests that G. japonica litter contains growth inhibitory substances. The extract was purified by chromatography while monitoring the inhibitory activity, and a growth inhibitory substance was isolated. The chemical structure of the substance was determined by spectral data to be a novel compound, 13-. O-β-fucopyranosyl-3β-hydroxymanool. This compound inhibited root and shoot growth of garden cress and barnyard grass at concentrations ranging from 89.7 to 271. μM for 50% inhibition. In addition, the compound had potent growth inhibitory activity with the soil taken from near the colony. The concentration of the compound in soil under a pure colony of G. japonica was 790. μM, suggesting that the compound may contribute to the establishment of monocultural stands by this fern.</p>

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Jahanyne, an apoptosis-inducing lipopeptide from the marine cyanobacterium lyngbya sp.

Iwasaki Arihiro, Ohno Osamu, Sumimoto Shinpei, Ogawa Hidetoshi, Nguyen Kim Anh, Suenaga Kiyotake

Organic Letters 17 ( 3 ) 652 - 655 2015.02

Accepted,  ISSN  1523-7060

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<p>An acetylene-containing lipopeptide, jahanyne, was isolated from the marine cyanobacterium Lyngbya sp. Its gross structure was established by spectroscopic analyses, and the absolute configuration was clarified based on a combination of chiral HPLC analyses, spectroscopic analyses, and derivatization reactions. Jahanyne significantly inhibited the growth of human cancer cells and induced apoptosis in HeLa cells.</p>

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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 2014.12

Accepted,  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) 2014.10

Accepted,  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 2014.07

Accepted,  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 2014.07

Accepted,  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 2014.07

Research paper (scientific journal), Accepted,  ISSN  0304-3770

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