Heterocyclic Compounds with 4 or More Rings

Publication Title: 
Oncology Reports

Silent information regulator 2 (SIR2) is a highly conserved protein, the mammalian orthologue of which, SIRT1, exhibits histone deacetylase activity. SIRT1 is involved not in only longevity due to caloric restriction but in a variety of diseases such as diabetes, cardiovascular dysfunction and neurodegeneration. However, accumulating evidence shows that SIRT1 is overexpressed in various types of malignant cells, and its inhibitors suppress the growth of tumor cells. The relationship between SIRT1 and metastasis remains to be clarified.

Author(s): 
Suzuki, Kensuke
Hayashi, Ryuji
Ichikawa, Tomomi
Imanishi, Shingo
Yamada, Toru
Inomata, Minehiko
Miwa, Toshiro
Matsui, Shoko
Usui, Isao
Urakaze, Masaharu
Matsuya, Yuji
Ogawa, Hirofumi
Sakurai, Hiroaki
Saiki, Ikuo
Tobe, Kazuyuki
Publication Title: 
Scientific Reports

Sirt1 is an NAD(+)-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet.

Author(s): 
Minor, Robin K.
Baur, Joseph A.
Gomes, Ana P.
Ward, Theresa M.
Csiszar, Anna
Mercken, Evi M.
Abdelmohsen, Kotb
Shin, Yu-Kyong
Cantó, Carles
Scheibye-Knudsen, Morten
Krawczyk, Melissa
Irusta, Pablo M.
Martin-Montalvo, Alejandro
Hubbard, Basil P.
Zhang, Yongqing
Lehrmann, Elin
White, Alexa A.
Price, Nathan L.
Swindell, William R.
Pearson, Kevin J.
Becker, Kevin G.
Bohr, Vilhelm A.
Gorospe, Myriam
Egan, Josephine M.
Talan, Mark I.
Auwerx, Johan
Westphal, Christoph H.
Ellis, James L.
Ungvari, Zoltan
Vlasuk, George P.
Elliott, Peter J.
Sinclair, David A.
de Cabo, Rafael
Publication Title: 
Expert Opinion on Therapeutic Patents

INTRODUCTION: Reversible acetylation is a key post-translational modification of target proteins. Sirtuin deacetylases represent the homolog of the yeast silent information regulator (SIR2). Although seven sirtuins have been found in mammals, all sirtuin activators described to date act through SIRT1.

Author(s): 
Villalba, JosÈ M.
de Cabo, Rafael
Alcain, Francisco J.
Publication Title: 
Bioorganic & Medicinal Chemistry Letters

Four 5-carbon-linked trioxane dimer orthoesters (6a-6d) have been prepared in 4 or 5 chemical steps from the natural trioxane artemisinin (1). When administered orally to malaria-infected mice using a single dose of only 6 mg/kg body weight along with 18 mg/kg of mefloquine hydrochloride, trioxane dimer orthoester sulfone 6d completely and safely cured the mice; after 30 days, the cured mice showed no detectable parasitemia, gained at least as much weight as the control mice (no infection), and behaved normally.

Author(s): 
Moon, Deuk Kyu
Tripathi, Abhai
Sullivan, David
Siegler, Maxime A.
Parkin, Sean
Posner, Gary H.
Publication Title: 
Journal of Natural Medicines

Shatavari-a famous Ayurveda materia medica used mainly as a tonic for women-is distributed in health food products all over the world. The Ayurvedic Pharmacopoeia of India identifies the botanical origin of shatavari as the tuberous root of Asparagus racemosus. We recently investigated by DNA analysis the botanical origin of shatavari products on the Japanese market. The results suggested that their botanical origin was Asparagus; however, species identification was difficult.

Author(s): 
Kumeta, Yukie
Maruyama, Takuro
Wakana, Daigo
Kamakura, Hiroyuki
Goda, Yukihiro
Publication Title: 
Journal of Natural Medicines

Shatavari-a famous Ayurveda materia medica used mainly as a tonic for women-is distributed in health food products all over the world. The Ayurvedic Pharmacopoeia of India identifies the botanical origin of shatavari as the tuberous root of Asparagus racemosus. We recently investigated by DNA analysis the botanical origin of shatavari products on the Japanese market. The results suggested that their botanical origin was Asparagus; however, species identification was difficult.

Author(s): 
Kumeta, Yukie
Maruyama, Takuro
Wakana, Daigo
Kamakura, Hiroyuki
Goda, Yukihiro
Publication Title: 
Journal of Agricultural and Food Chemistry

Trifolirhizin, a pterocarpan flavonoid, was isolated from the roots of Sophora flavescens, and its chemical structure was confirmed by (1)H and (13)C NMR and MS spectra. Its anti-inflammatory activity was examined in lipopolysaccharide (LPS)-stimulated mouse J774A.1 macrophages. Trifolirhizin not only dose-dependently inhibited LPS-induced expression of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) but also inhibited lipopolysaccharide (LPS)-induced expression of cyclooxygenase-2 (COX-2).

Author(s): 
Zhou, Huiping
Lutterodt, Herman
Cheng, Zhihong
Yu, Liangli Lucy
Publication Title: 
The Journal of Biological Chemistry

Blockade of excessive Toll-like receptor (TLR) signaling is a therapeutic approach being actively pursued for many inflammatory diseases. Here we report a Chinese herb-derived compound, sparstolonin B (SsnB), which selectively blocks TLR2- and TLR4-mediated inflammatory signaling. SsnB was isolated from a Chinese herb, Spaganium stoloniferum; its structure was determined by NMR spectroscopy and x-ray crystallography.

Author(s): 
Liang, Qiaoli
Wu, Qinan
Jiang, Jihong
Duan, Jin'ao
Wang, Chao
Smith, Mark D.
Lu, Hong
Wang, Qian
Nagarkatti, Prakash
Fan, Daping
Publication Title: 
Scientific Reports

Sirt1 is an NAD(+)-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet.

Author(s): 
Minor, Robin K.
Baur, Joseph A.
Gomes, Ana P.
Ward, Theresa M.
Csiszar, Anna
Mercken, Evi M.
Abdelmohsen, Kotb
Shin, Yu-Kyong
Cantó, Carles
Scheibye-Knudsen, Morten
Krawczyk, Melissa
Irusta, Pablo M.
Martin-Montalvo, Alejandro
Hubbard, Basil P.
Zhang, Yongqing
Lehrmann, Elin
White, Alexa A.
Price, Nathan L.
Swindell, William R.
Pearson, Kevin J.
Becker, Kevin G.
Bohr, Vilhelm A.
Gorospe, Myriam
Egan, Josephine M.
Talan, Mark I.
Auwerx, Johan
Westphal, Christoph H.
Ellis, James L.
Ungvari, Zoltan
Vlasuk, George P.
Elliott, Peter J.
Sinclair, David A.
de Cabo, Rafael
Publication Title: 
Archives of Pharmacal Research

Sparstolonin B (SsnB) is an isocoumarin compound isolated from the tubers of both Sparganium stoloniferum and Scirpus yagara. We previously demonstrated that SsnB blocked the Toll-like receptor (TLR) 2- and TLR4-triggered inflammatory signaling in macrophages by inhibiting the recruitment of MyD88 to the TIR domains of TLR2 and TLR4. The present study was designed to examine the effects of SsnB on vascular inflammatory responses in human umbilical vein endothelial cells (HUVECs) challenged by lipopolysaccharide (LPS, a TLR4 ligand).

Author(s): 
Liang, Qiaoli
Yu, Fang
Cui, Xiaodong
Duan, Jin'ao
Wu, Qinan
Nagarkatti, Prakash
Fan, Daping

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