Halogenated cladosporols produced by the sodium halide-supplemented fermentation of the plant-associated fungus Cladosporium sp. TMPU1621.
Yamazaki H, Yagi A, Akaishi M, Kirikoshi R, Takahashi O, Abe T, Chiba S, Takahashi K, Iwakura N, Namikoshi M, Uchida R.
Tetrahedron Lett. 2018; 59: 1913–1915 (Selected as a front cover of this issue).
A new cladosporol derivative, 2-chloro-cladosporol D (6), was isolated together with known cladosporol (1), cladosporols B–D (2–4), and cladosporol F (5) from the culture broth of plant-associated Cladosporium sp. TMPU1621. The structure of 6 was elucidated from spectroscopic analyses including NMR and MS data. The productivity of 6 increased in 3% NaCl-supplemented medium; therefore, fermentation of the producing fungus TMPU1621 with 3% NaBr was investigated, leading to the induced production of a new halogenated cladosporol, 2-bromo-cladosporol D (7). Compound 2 showed the lowest MIC values of 3.13 and 12.5 lg/mL against two MRSA strains, ATCC43300 and ATCC700698, respectively.
Bioactivity of extracts from ascidians collected in North Sulawesi as seeds of marine-derived drugs.
Sumilat DA, Wewengkang DS, Rotinsulu H, Yamazaki H, Oda T, Ukai K, Namikoshi M.
AACL Bioflux 2018; 11: 516–524.
The ethanol extracts from 95 ascidians collected at North Sulawesi in 2010 were evaluated for their inhibitory activity against the colony formation of Chinese hamster V79 cells, proliferation of two human cancer cell lines (colon HCT-15 and T-cell lymphoma Jurkat), and the growth of Staphylococcus aureus (Gram-positive bacterium), Escherichia coli (Gram-negative bacterium), Candida albicans (yeast), and Mucor hiemalis (filamentous fungus). Thirty-eight extracts showed the inhibitory effects (> 50% at 50 μg mL-1) on V79 cells, and 13 and 15 extracts were active (> 50%) against HCT-15 and Jurkat cells, respectively. Among 13 extracts, five extracts were selectively active against HCT-15 cells. Five extracts showed both cytotoxic and antimicrobial activities. The growth of S. aureus, E. coli, C. albicans, and M. hiemalis was inhibited by seven, one, five, and nine extracts, respectively. Among nine extracts, seven extracts were active only on M. hiemalis. Two compounds, shermilamine B (1) and kuanoniamine D (2), were isolated from Cystodytes sp. as cytotoxic components. Compound 1 was selectively active against HCT-15 (IC50 = 6.7 μM) with no apparent effect on V79 and Jurkat. Compound 2 inhibited HCT-15 (IC50 = 4.1 μM) and Jurkat (19.0 μM) cells, and the EC50 value against V79 cells was 6.2 μM.
Absolute structures of wedelolide derivatives and structure-activity relationships of protein tyrosine phosphatase 1B inhibitory ent-kaurene diterpenes from aerial parts of Wedelia spp. collected in Indonesia and Japan.
Abdjul DB, Yamazaki H, Kanno S, Kirikoshi R, Tomizawa A, Takahashi O, Maarisit W, Losung F, Rotinsulu H, Wewengkang DS, Sumilat DA, Kapojos MM, Namikoshi M.
Chem Pharm Bull. 2018; 66: 682–687.
Two sesquiterpene lactones with the (9R)-eudesman-9,12-olide framework, wedelolides I and J, have been isolated together with five eudesmanolide sesquiterpenes and twelve ent-kaurene diterpenes from the aerial parts of Indonesian Wedelia prostrata. The absolute configurations of wedelolides I and J, proposed in the previous communication, were proven by comparing their experimental Electronic Circular Dichroism (ECD) spectra with the calculated ECD spectrum of wedelolide I. The phytochemical study on the aerial parts of Okinawan Wedelia chinensis led to the isolation of three other eudesmanolide sesquiterpenes in addition to the three sesquiterpenes and eleven diterpenes isolated from the Indonesian W. prostrata as above. However, the wedelolide derivatives found in the Indonesian plant were not detected. Among these compounds, most of the diterpenes inhibited protein tyrosine phosphatase (PTP) 1B activity, and a structure-activity relationship study revealed that the cinnamoyl group enhanced inhibitory activity. Therefore, two ent-kaurene derivatives with and without a cinnamoyl group were examined for the ability to accumulate phosphorylated-Akt (p-Akt) because PTP1B dephosphorylates signal transduction from the insulin receptor such as phosphorylated Akt, a key downstream effector. However, neither compound enhanced insulin-stimulated p-Akt levels in two human hepatoma cell lines (Huh-7 and HepG2) at non-cytotoxic doses.
Celludinones, new inhibitors of sterol O-acyltransferase, produced by Talaromyces cellulolyticus BF-0307.
Ohshiro T, Seki R, Fukuda T, Uchida R, Tomoda H.
J Antibiot . 2018; 71: 1000-1007.
New indanones, designated celludinones A ((±)-1) and B (2), were isolated from the culture broth of the fungal strain Talaromyces cellulolyticus BF-0307. The structures of celludinones were elucidated by spectroscopic data, including 1D and 2D NMR. Celludinone A was found to be a mixture of racemic isomers ((±)-1), which were isolated by a chiral column. Compounds (+)-1 and (-)-1 inhibited the sterol O-acyltransferase (SOAT) 1 and 2 isozymes in a cell-based assay using SOAT1- and SOAT2-expressing Chinese hamster ovary (CHO) cells, while 2 selectively inhibited the SOAT2 isozyme.
Anti-Rhizopus activity of tanzawaic acids produced by the hot spring-derived fungus Penicillium sp. BF-0005.
Tominaga T, Uchida R, Koyama N, Tomoda H.
J Antibiot . 2018; 71: 626-632.
A silkworm infection assay with the pathogenic fungus Rhizopus oryzae was established. Microbial culture broths were screened for anti-Rhizopus antibiotics using this assay. A new compound, tanzawaic acid R was isolated along with known and structurally related tanzawaic acids and arohynapene A from the culture broth of the hot spring-derived fungus Penicillium sp. BF-0005. The structure of tanzawaic acid R was elucidated by various spectroscopic data including 1D and 2D nuclear magnetic resonance spectroscopy. Tanzawaic acids A, B, C, and R and arohynapene A exhibited antifungal activity against R. oryzae. Tanzawaic acids A and B dose-dependently exerted therapeutic effects in the silkworm infection assay with R. oryzae.
A new protein tyrosine phosphatase 1B inhibitory α-pyrone-type polyketide from Okinawan plant-associated Aspergillus sp. TMPU1623
Yamazaki H, Takahashi K, Iwakura N, Abe T, Akaishi M, Chiba S, Namikoshi M, Uchida R.
J Antibiot. 2018; 71: 745-748.
A new polyenyl-α-pyrone polyketide, aspopyrone A (1), was isolated from a culture broth of Okinawan plant-associated Aspergillus sp. TMPU1623 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was assigned based on NMR experiments. Compound 1 exhibited protein tyrosine phosphatase (PTP) 1B and T-cell PTP (TCPTP) inhibitory activities with IC50 values of 6.7 and 6.0 μM, respectively.
Callyspongiamides A and B, sterol O-acyltransferase inhibitors, from the Indonesian marine sponge Callyspongia sp.
Kapojos MM, Abdjul DB, Yamazaki H, Ohshiro T, Rotinsulu H, Wewengkang DS, Sumilat DA, Tomoda H, Namikoshi M, Uchida R.
Bioorg Med Chem Lett. 2018; 28: 1911-1914.
Callyspongiamides A (1) and B (2), two new sterol O-acyltransferase (SOAT) inhibitors, were isolated from the Indonesian marine sponge Callyspongia sp. together with a known congener, dysamide A (3). The structures of 1 and 2 were elucidated to be polychlorine-containing modified dipeptides based on their spectroscopic data. Compounds 1-3 inhibited both of the SOAT isozymes, SOAT1 and SOAT2, in cell-based and enzyme-based assays.
Cladosporamide A, a new protein tyrosine phosphatase 1B inhibitor, produced by an Indonesian marine sponge-derived Cladosporium sp.
Rotinsulu H, Yamazaki H, Sugai S, Iwakura N, Wewengkang DS, Sumilat DA, Namikoshi M
J Nat Med. 2018; 72: 779–783.
Cladosporamide A (1), a new protein tyrosine phosphatase (PTP) 1B inhibitor, was isolated together with a known prenylated flavanone derivative (2) from the culture broth of an Indonesian marine sponge-derived Cladosporium sp. TPU1507 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was elucidated based on 1D and 2D NMR data. Compound 1 modestly inhibited PTP1B and T-cell PTP (TCPTP) activities with IC50 values of 48 and 54 μM, respectively. The inhibitory activity of 2 against PTP1B (IC50 = 11 μM) was approximately 2-fold stronger than that against TCPTP (IC50 = 27 μM).
Anti-mycobacterial haliclonadiamine alkaloids from the Okinawan marine sponge Haliclona sp. collected at Iriomote Island.
Abdjul DB, Yagi A, Yamazaki H, Kirikoshi R, Takahashi O, Namikoshi M, Uchida R
Phytochem Lett. 2018; 26: 130-133.
Two new haliclonadiamine derivatives, halichondriamine C (1) and 1-epi-halichondriamine C (2), were isolated from the Okinawan marine sponge Haliclona sp. together with known haliclonadiamine (3) and papuamine (4). The structures of 1 and 2 were elucidated based on their spectroscopic data by comparisons with those for related compounds. Compounds 1 and 2 were epimers of each other at the C-1 position. Compounds 1–4 inhibited the growth of Mycobacterium smegmatis and M. bovis BCG and exhibited antibacterial activities against M. avium and M. intracellulare as pathogens of M. avium complex (MAC) disease.
Protein tyrosine phosphatase 1B inhibitory components and a new unique N-alkylamide derivative with an endoperoxide bridge from aerial parts of Indonesian Spilanthes paniculata
Abdjul DB, Yamazaki H, Maarisit W, Kirikoshi R, Takahashi O, Losung F, Kapojos MM, Namikoshi M.
Phytochem Lett. 2018; 26: 71-74.
Research on protein tyrosine phosphatase (PTP) 1B inhibitors from terrestrial and marine natural resources identified N-isobutyl-2E-decenamide (1) and 3,4,5-tri-O-caffeoylquinic acid (2) as PTP1B inhibitory substances together with a new N-alkylamide (3) and two known congeners (4 and 5) from the aerial parts of Indonesian Spilanthes paniculata. The structure of 3 was elucidated as (2E, 7Z)-6,9-endoperoxy-N-2-methylbutyl-2,7-decadienamide based on its spectroscopic data. Compound 3 is a rare N-alkylamide derivative with an endoperoxide bridge, and only three natural products have been reported in this class. Compound 1 inhibited PTP1B activity with an IC50 value of 24 μM, whereas compound 2 exerted an inhibitory effect of 35% at 15 μM. This is the first study to report the inhibitory effects of an N-alkylamide derivative (1) on PTP1B activity.
Protein tyrosine phosphatase 1B inhibitory polybromobiphenyl ethers and monocyclofarnesol-type sesquiterpenes from the Indonesian marine sponge cf.
Kapojos MM, Abdjul DB, Yamazaki H, Kirikoshi R, Takahashi O, Rotinsulu H, Wewengkang DS, Sumilat DA, Ukai K, Namikoshi M.
Phytochem Lett. 2018; 26: 10-14.
Three known polybromobiphenyl ether derivatives, 2-(2′,4′-dibromophenoxy)-3,5-dibromophenol (1), 2-(2′,4′-dibromophenoxy)-4,6-dibromophenol (2), and 2-(2′-dibromophenoxy)-3,4,5,6-tetrabromophenol (3), were identified as PTP1B inhibitors from the Indonesian marine sponge Lamellodysidea sp. (cf. L. herbacea) together with two new monocyclofarnesol-derived sesquiterpenes, lamellolactones A (4) and B (5). The structures of 4 and 5 were elucidated based on their spectroscopic data and comparisons with those for related compounds. Compounds 1–3 inhibited PTP1B activity with IC50 values of 5.3, 7.8, and 5.3 μM, respectively, while compounds 4 and 5 were not active at 38–40 μM. The selective activities of 1–3 against PTP1B over the other PTPs (T-cell PTP, CD45 tyrosine phosphatase, and vaccinia H-1-related phosphatase) showed that the position and/or number of Br atoms affected their inhibitory activities.
第 15 回棘皮動物研究集会: 横浜 平成 30 年 12 月
鵜飼 和代，工藤 香澄，浪越 通夫
第 44 回反応と合成の進歩シンポジウム: 熊本 平成 30 年 11 月
Amphotericin B 活性増強作用を有する simpotentin の全合成と絶対立体配置の決定
大多和 正樹，清水 恵理，齋藤 淳，李 大葵，近藤 あり子，八木 瑛穂，小林 啓介，内田 龍児，供田 洋，長光 亨
12th International BMP conference: Tokyo, 平成 30 年 10 月
Isolation and characterization of small molecule inhibitors of BMP induced osteoblastic differentiation from the Indonesian marine sponge.
Ohte S, Yamazaki H, Rotinsulu H, Wewengkang DS, Sumilat DA, Uchida R, Namikoshi M, Katagiri T, Tomoda H
第 57 回日本薬学会東北支部大会: 仙台 平成 30 年 10 月
Oleanane 型トリテルペン化合物類の SOAT2 阻害活性
大城 太一，関 怜子，山﨑 寛之，Delfly B. Abdjul，内田 龍児，浪越 通夫，供田 洋
渡辺 栞，三浦 夢咲，内田 龍児，藤村 務
カイコを宿主とした Mycobacterium avium complex 症モデルの構築
八木 瑛穂，内田 龍児
第 60 回天然有機化合物討論会: 久留米 (福岡) 平成 30 年 9 月
真菌が生産するアムホテリシン B 活性増強物質 simpotentin に関する研究
内田 龍児，大多和 正樹，近藤 あり子，清水 恵理，八木 瑛穂，齊藤 惇，李 大葵，小林 啓介，野中 健一，増間 碌郎，長光 亨，供田 洋
1st International Seminar on Pharmaceutical 2018: Manado (Indonesia), 平成 30 年 9 月
Anti-mycobacterial activity from the marine sponge Haliclona sp.
Maarisit W, Yamazaki H, Ukai K, Namikoshi M
ASM Microbe 2018, Atlanta, USA, 2018 年 6 月
A new potentiator of antifungal activity of amphoricin B against Candida albicans, produced by Simplicillium minatense FKI-4981
Uchida R, Kobayashi K, Nonaka K, Masuma R, Nagamitsu T, Tomoda H
16th International Echinoderm Conference, Nagoya, 2018 年 5 月
Identification of autotomy-promoting factor from a Japanese sea star Asterias amurensis and mechanism of autotomy
Ukai K, Namikoshi M
日本薬学会第 138 年会: 金沢 (石川) 平成 31 年 3 月 25 日~28 日
植物内生糸状菌Cladosporium sp.TMPU 1621 株が生産する抗生物質およびハロゲン化物塩を用いた新規類縁体の生産誘導
八木 瑛穂, 赤石 将成, 桐越 亮太, 高橋 央宜, 阿部 樹, 高橋 健太, 千葉 聡美, 山崎 寛之, 内田 龍児
新奇な構造を有する放線菌由来 scopranone 類の生合成研究
出町 歩, 内田 龍児, 新家 一男, 池田 治生, 供田 洋
インドネシアおよび八重山諸島産 Lantana camara より得られた oleanane 型トリテルペンの構造と protein tyrosine phosphatase 1B 阻害活性
山﨑寛之, Delfly B. Abdjul a, Wilmar Maarisit b, Henki Rotinsulu b, Defny S. Wewengkang b, Deiske A. Sumilat b, Magie M. Kapojos c, Fitje Losung b, 浪越通夫
紺谷 深雪, 下山 健太, 内田 龍児, 供田 洋, 長光 亨
第 34 回東北医科薬科大学生涯教育講演会，仙台，2018 年 2 月 24 日