Ktedonoketone and 2'-oxosattabacin, benzenoid metabolites from a thermophilic bacterium Thermosporothrix hazakensis in the phylum Chloroflexi.

A thermophilic bacterium Thermosporothrix hazakensis NBRC 105916 which belongs to the class Ktedonobacteria was investigated to explore its biosynthetic potential of secondary metabolites. UV-guided fractionation led to the identification of a new benzenoid metabolite designated ktedonoketone (6) and an α-diketone metabolite 2'-oxosattabacin (7) along with five known compounds. Compound 7 was previously described as a synthetic compound, but this is the first finding as a natural product.

Two new secondary metabolites from a fungus of the genus Robillarda.

Two new compounds, robillafuran and (+)-robillapyrone, were isolated from the culture extract of a fungal strain of Robillarda along with (+)-monascuspyrone. The absolute configuration of (+)-robillapyrone and (+)-monascuspyrone was determined by ECD calculation. These three compounds showed preadipocyte differentiation activity at 10-40 μM.

Simamycin (5'-O-geranyluridine): a new prenylated nucleoside from Streptomyces sp.

A new nucleoside modified by prenylation, simamycin (1), was isolated from the culture broth of a soil-derived Streptomyces sp. Its structure was determined by spectroscopic analysis and chemical synthesis as 5'-O-geranyluridine. Compound 1 induced differentiation of preadipocytes into matured adipocytes.

[Food Application of Newly Developed Handy-type Glutamate Sensor].

Tests on physiological functions of umami have been actively conducted and a need recognized for a high-performance quantification device that is simple and cost-effective, and whose use is not limited to a particular location or user. To address this need, Ajinomoto Co. and Tanita Corp.

Hikiamides A-C, Cyclic Pentadepsipeptides from Fusarium sp. TAMA 456.

Three new cyclic pentadepsipeptides, hikiamides A-C (1-3), were isolated from the culture extract of Fusarium sp. TAMA 456. The structures were determined by spectroscopic analysis using NMR and MS, and the absolute configurations were established by using Marfey's method and chiral HPLC analysis.

Nocapyrones: α- and γ-pyrones from a marine-derived Nocardiopsis sp.

One new α-pyrone (nocapyrone R (1)), and three known γ-pyrones (nocapyrones B, H and L (2-4)) were isolated from the culture extract of a Nocardiopsis strain collected from marine sediment. Structures of these compounds were determined on the basis of spectroscopic data including NMR and MS. γ-Pyrones 2-4 were found to induce adiponectin production in murine ST-13 preadipocyte cells but the α-pyrone 1 had no activity.

Jomthonic acid , a modified amino acid from a soil-derived Streptomyces.

Jomthonic acid A (1), a new modified amino acid, was isolated from the culture broth of a soil-derived actinomycete of the genus Streptomyces. The structure and absolute configuration of 1 were determined by spectroscopic analyses and chemical conversion. Jomthonic acid A (1) induced differentiation of preadipocytes into mature adipocytes at 2-50 μM.

Norlichexanthone isolated from fungus P16 promotes the secretion and expression of adiponectin in cultured ST-13 adipocytes.

Adiponectin, an adipose-derived protein, shows insulin-sensitizing, anti-diabetic and anti-atherogenic activities, which implies that the protein represents a potential target to improve lifestyle-related diseases like type 2 diabetes. Based on our hypothesis that agents that cause adipocyte differentiation could also act as adiponectin secretion enhancers, we screened butanol extracts of 96 fungus culture extracts for their differentiation-inducing activity in ST-13 preadipocytes. We found that the butanol extract of a fungus P16 culture extract possessed such an activity, and isolated norlichexanthone as an active compound through activity-guided fractionation.

Nobiletin, a citrus polymethoxyflavonoid, suppresses multiple angiogenesis-related endothelial cell functions and angiogenesis in vivo.

Nobiletin is a citrus polymethoxyflavonoid that suppresses tumor growth and metastasis, both of which depend on angiogenesis. We recently identified nobiletin as a cell differentiation modulator. Because cell differentiation is a critical event in angiogenesis, it might be possible that nobiletin could exhibit antiangiogenic activity, resulting in suppression of these tumor malignant properties.

Identification of nobiletin, a polymethoxyflavonoid, as an enhancer of adiponectin secretion.

Adiponectin, an adipocyte-derived protein with insulin-sensitizing, anti-diabetic and anti-atherogenic activities, is known to be induced during adipocyte differentiation. Nobiletin, a citrus polymethoxy flavonoid, was found to induce the differentiation of ST-13 preadipocytes into mature adipocytes and enhance the production of adiponectin protein at a concentration of 10 microM.

A new antiangiogenic C24 oxylipin from the soft coral Sinularia numerosa.

A new oxylipin, 15-hydroxy-tetracosa-6,9,12,16,18-pentaenoic acid (15-HTPE; 1) was isolated as an inhibitor of tube-formation from the soft coral Sinularia numerosa. Its structure was elucidated by means of spectral analysis and chemical degradation. 15-HTPE inhibited tube formation of EA.

Dipalmitoylation of radicicol results in improved efficacy against tumor growth and angiogenesis in vivo.

Tumor-related angiogenesis is likely to be a potential target for the treatment of cancer. One key to develop this angiostatic strategy would be to find useful angiogenesis inhibitors. Here we report the effects of radicicol, a microbial angiogenesis inhibitor that we previously identified using the chorioallantoic membrane assay, and its novel analog, 14,16-dipalmitoyl-radicicol, on tumor angiogenesis and growth.

Suppression of laser-induced choroidal neovascularization by subconjunctival injection of 9alpha-fluoromedroxyprogesterone acetate (FMPA), an anti-angiogenic agent, in rats.

9alpha-Fluoromedroxyprogesterone acetate (FMPA) is a synthetic analog of medroxyprogesterone acetate (MPA). FMPA exhibited more potent anti-tumor and anti-angiogenic activities in some assay systems than the parent agent, MPA. Exudative age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV).

Synthesis and anti-tumor activity of a fluorinated analog of medroxyprogesterone acetate (MPA), 9alpha-fluoromedroxyprogesterone acetate (FMPA).

We synthesized 9alpha-fluoromedroxyprogesterone acetate (FMPA) in order to test whether it is a more potent anti-angiogenic agent than medroxyprogesterone acetate (MPA), which has been widely used as a therapeutic agent for breast and endometrium cancers. FMPA was previously synthesized in 10 steps (total yield: 1%). An efficient synthesis of FMPA has been achieved in 6 steps (total yield: 12%).

Inhibition of in vivo angiogenesis by N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine.

N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), an antibacterial substance isolated from the flesh fly, inhibits human tumor growth in the nude mice model; however, the mechanism of its action is unclear. The in vivo antitumor effect includes the inhibition of tumor cell proliferation and suppression of angiogenesis. Angiogenesis is essential for tumor growth in vivo.

Directed biosynthesis of fluorinated pseurotin A, synerazol and gliotoxin.

Aspergillus fumigatus TP-F0196 produces pseurotin A, synerazol and gliotoxin. Phenylalanine is a common biosynthetic precursor of these antibiotics. Feeding fluorophenylalanine to the culture induced the production of novel fluorinated analogs.

Bovine lactoferrin inhibits tumor-induced angiogenesis.

Recent studies have demonstrated that bovine lactoferrin (bLF) suppresses tumor growth and metastasis in the mouse and rat and moreover may inhibit angiogenesis. To determine whether angiogenesis inhibition might contribute to antitumor activity, we examined the influence of bLF on tumor-induced angiogenesis and endothelial cell functions as well as angiogenesis-related cytokine production. Bovine LF exhibited dose-dependent inhibition of angiogenesis on 4-6-day-old chick embryo chorioallantoic membranes (CAMs) that lack a mature immune response.

Novel function of ascorbic acid as an angiostatic factor.

Endothelial permeability is increased by vascular endothelial cell growth factor and decreased by antioxidants. Whether or not l-ascorbic acid (Asc), which decreases endothelial permeability by stimulating the endothelial barrier function, is anti-angiogenic (angiostatic) remains unknown. We examined the role of Asc on angiogenesis using two assay systems.

Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo.

We previously showed pomegranate seed oil and fermented juice polyphenols to retard oxidation and prostaglandin synthesis, to inhibit breast cancer cell proliferation and invasion, and to promote breast cancer cell apoptosis. Here we evaluated the anti-angiogenic potential of these materials in several ways. We checked a possible effect on angiogenic regulation by measuring vascular endothelial growth factor (VEGF), interleukin-4 (IL-4) and migration inhibitory factor (MIF) in the conditioned media of estrogen sensitive (MCF-7) or estrogen resistant (MDA-MB-231) human breast cancer cells, or immortalized normal human breast epithelial cells (MCF-10A), grown in the presence or absence of pomegranate seed oil (SESCO) or fermented juice polyphenols (W).