Hikaru Kato

Isolation of Antipodal (−)-Versicolamide B and Notoamides L−N from a Marine-Derived Aspergillus sp.

Antipodal (-)-versicolamide B and notoamides L-N were isolated from a marine-derived Aspergillus sp. The possible biosynthetic pathway of enantiomeric pairs of notoamide B and versicolamide B are proposed. Notoamide L is the first metabolite containing 25 carbons in the related prenylated indole alkaloids. Notoamide M is potentially a precursor to the proposed azadiene species involved in the putative intramolecular Diels-Alder reaction in the biogenesis of the bicyclo[2.2.2]diazaoctane ring system.

Notoamides F-K, prenylated indole alkaloids isolated from a marine-derived Aspergillus sp.

Six new prenylated indole alkaloids, named notoamides F-K (8-13), were isolated from a marine-derived Aspergillus sp. Their structures, including absolute configurations, were elucidated by spectroscopic methods. Notoamide I (11) showed weak cytotoxicity against HeLa cells with an IC(50) value of 21 microg/mL.

Isolation of Notoamide E, a Key Precursor in the Biosynthesis of Prenylated Indole Alkaloids in a Marine-Derived Fungus, Aspergillus sp.

Notoamide E was identified to be a short-lived precursor in the biosynthesis of prenylated indole alkaloids in the mussel-derived Aspergillus sp. In addition, the feeding experiment of the (13)C-labeled notoamide E afforded structurally novel metabolites.

Stilbenoids from the Melinjo (Gnetum gnemon L.) Fruit Modulate Cytokine Production in Murine Peyer's Patch Cells Ex Vivo

Melinjo fruit ( Gnetum gnemon L.) has been used as a food in Southeast Asia. To investigate if this fruit has regulatory actions on ileal immune responses, we measured T-helper (Th) cytokine production, i.e., interleukin-2 (IL-2), IL-4, IL-5, and interferon-gamma (IFN- γ), in cultured Peyers patch (PP) cells from mice orally treated with a methanol extract of melinjo fruit. Oral administration of the 50 % ethanol extract at 100 mg/kg/day significantly enhanced the production of the Th1 cytokines IL-2 and IFN- γ irrespective of concanavalin-A stimulation, whereas the production of the Th2 cytokines IL-4 and IL-5 was not affected. We also isolated seven active constituents accompanied with two new stilbenoids from the ethylacetate fraction of the extracts. The structure of the new stilbene glucosides gnemonoside L (5) and gnemonoside M (7) was determined by 1D and 2Du2009NMR and MS analyses. Five known stilbenoids were identified as resveratrol (1), isorhapontigenin (2), gnemonoside D (4), gnetins C (3) and E (6). Among these tested compounds, only new stilbenoid 7 strongly enhanced Th1 cytokine production in cultured PP cells at 10 mg/kg/day. These results indicated that this melinjo extract and its active constituent 7 potentiated T-cell-dependent immune responses in the ileal mucosa.

Anti-inflammatory constituents from Tabebuia avellanedae

Five novel compounds were isolated from the water extract of Tabebuia avellanedae, and their structures were established by analysis of NMR spectroscopy and mass spectrometry. Compounds 1-5 at 25μM showed strong inhibitory activity on the inflammatory cytokine, tumor-necrosis factor-α and interleukin-1β production in cultured human myeloma THP-1 cells co-stimulated with lipopolysaccharide without any significant cytotoxicity, and their anti-allergic and antioxidant activities were evaluated.

Phenolic lipid ingredients from cashew nuts

Five new phenolic lipids, 2-(8″Z-eicosenoyl)-6-(8′Z-pentadecenyl) salicylic acid (3), 2-(9″Z-hexadecenoyl)-6-(8′Z, 11′Z-pentadecadienyl) methyl salicylate (5), 2-(10″Z, 13″Z-nonadecadienoyl)-6-(8′Z, 11′Z-pentadecadienyl) salicylic acid (6), 2-(16″Z-pentacosenoyl)-6-(8′Z-pentadecenyl) salicylic acid (7) and 2-(9″Z-octadecenoyl)-6-(8′Z, 11′Z-pentadecadienyl) methyl salicylate (8), and three known compounds, cardols (1), anacardic acid (2) and cardanols (4), were isolated from the nuts of the cashew, Anacardium occidentale L. The structures were established on the basis of detailed MS and NMR spectroscopic analyses. Compound 1 highly enhanced both Th-1 (IL-2, IFN-γ) and Th-2 (IL-4, IL-5) cytokine production, and compounds 7 and 8 highly increased cytokine IL-2 and IFN-γ production in response to concanavalin A in cultured murine Peyer’s patch cells ex vivo. The isolated compounds showed moderate inhibitory activities on cytochrome CYP3A4 enzyme.

CYP3A4 inhibitors isolated from a marine derived fungus Penicillium species

Abstract More than 50% of clinically used drugs are thought to be metabolized by cytochrome P450 (CYP) 3A4. Discovery of new, inexpensive, CYP3A4 inhibitors will reduce drug dosages needed to cure patients. In our search for new inhibitors of the enzyme CYP3A4, extracts from 102 marine fungi were screened. Seven of the extracts had potent CYP3A4 inhibitory activity. Four aromatic compounds were isolated from an extract of a culture of one of these, a Penicillium sp., and were identified as 3-methoxyphenol (1), 4-methoxyphenylacetic acid (2), 4-(2-hydroxyethyl)phenol (3), and 4-hydroxy-2-methoxyacetanilide (4) by use of spectroscopic data. Interestingly, compound 3 at 250xa0μgxa0mL−1did not inhibit CYP3A4 whereas compounds 1, 2 and 4 had CYP inhibitory activity with IC50 values of 2.0, 1.6 and 0.41xa0μgxa0mL−1, respectively.

Neurotrophic sesterterpenes isolated from a marine sponge, Spongia sp.

The MeOH extract of a marine sponge of the genus Spongia showed neurotrophic activity in pheochromocytoma (PC-12) cells. Purification of the extract afforded a new sesterterpene, deacetoxyscalarin (1), along with five known sesterterpenes (2-6). Among them, 2-6 induced neurite outgrowth in PC-12 cells at the concentration of 50 μg/mL but 1 was inactive.