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91.
Yuusuke Tamura Kyouhei Hayashi Naoki Omori Yuji Nishiura Kana Watanabe Nobuyuki Tanaka Masahiko Fujioka Naoki Kouyama Akira Yukimasa Yukari Tanaka Takeshi Chiba Hideki Tanioka Hirohide Nambu Hideo Yukioka Hiroki Sato Takayuki Okuno 《Bioorganic & medicinal chemistry letters》2013,23(1):90-95
Optimization of HTS hit 1 for NPY Y5 receptor binding affinity, CYP450 inhibition, solubility and metabolic stability led to the identification of some orally available oxygen-linker derivatives for in vivo study. Among them, derivative 4i inhibited food intake induced by the NPY Y5 selective agonist, and chronic oral administration of 4i in DIO mice caused a dose-dependent reduction of body weight gain. 相似文献
92.
Takako Aboshi Nobuhiro Shimizu Yuji Nakajima Yoshiyuki Honda Yasumasa Kuwahara Hiroshi Amano Naoki Mori 《Insect biochemistry and molecular biology》2013,43(11):991-996
We report here that Tyrophagus similis and Tyrophagus putrescentiae (Astigmata: Acaridae) have the ability to biosynthesize linoleic acid [(9Z, 12Z)-9, 12-octadecadienoic acid] via a Δ12-desaturation step, although animals in general and vertebrates in particular appear to lack this ability. When the mites were fed on dried yeast enriched with d31-hexadecanoic acid (16:0), d27-octadecadienoic acid (18:2), produced from d31-hexadecanoic acid through elongation and desaturation reactions, was identified as a major fatty acid component of phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) in the mites. The double bond position of d27-octadecadienoic acid (18:2) of PCs and PEs was determined to be 9 and 12, respectively by dimethyldisulfide (DMDS) derivatization. Furthermore, the GC/MS retention time of methyl 9, 12-octadecadienoate obtained from mite extracts agreed well with those of authentic linoleic acid methyl ester. It is still unclear whether the mites themselves or symbiotic microorganisms are responsible for inserting a double bond into the Δ12 position of octadecanoic acid. However, we present here the unique metabolism of fatty acids in the mites. 相似文献
93.
Kenji Sugimoto Kosuke Tamura Chihiro Tohda Naoki Toyooka Hideo Nemoto Yuji Matsuya 《Bioorganic & medicinal chemistry》2013,21(15):4459-4471
As an extended study on development of anti-Alzheimer’s disease agent, we newly synthesized various dihydrofuran-fused perhydrophenanthrenes via o-quinodimethane chemistry. This study revealed that the introduction of carbon side-chain on 8-position or removal of the acetal moiety on 3-position arose a cytotoxicity on rat cortical neurons. On the other hand, the ethereal or thio-ethereal substituent on 8-position enhanced the elongation effect on Aβ-damaged neurons. The necessity of the cyano group on 10b position was also proved in this structure–activity-relationship study. 相似文献
94.
Yuji Nakamura Teppei Fujimoto Yasuyuki Ogawa Hidenori Namiki Sayaka Suzuki Masayoshi Asano Chie Sugita Akiyoshi Mochizuki Shojiro Miyazaki Kazuhiko Tamaki Yoko Nagai Shin-ichi Inoue Takahiro Nagayama Mikio Kato Katsuyoshi Chiba Kiyoshi Takasuna Takahide Nishi 《Bioorganic & medicinal chemistry》2013,21(11):3175-3196
With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure–activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h. 相似文献
95.
Keiju Okano Takeshi Nakamura Yuji Kamiya Susumu Ikegami 《Bioscience, biotechnology, and biochemistry》2013,77(3):805-807
Cultured crown gall cells of Catharanthus roseus Don (Vinca rosea L.) was found to contain brassinosteroids. These were identified as brassinolide and castasterone by GC/MS. This is the first conclusive identification of endogenous brassinosteroids in cultured cells. 相似文献
96.
Kojiro Wada Yuji Enomoto Katsura Munakata 《Bioscience, biotechnology, and biochemistry》2013,77(6):946-953
Shiromodiol-diacetate, shiromool, and shiromodiol-monoacetate are insect feeding inhibitors isolated from Parabenzoin trilobum Nakai. On the bases of chemical and spectral evidence we deduced that these compounds have the structure shown in I, XVIII, and XI, respectively. 相似文献
97.
Yuji Koide Mamoru Honma Tokuji Shimomura 《Bioscience, biotechnology, and biochemistry》2013,77(3):775-776
Modified fungal product 4-O-methylascochlorin (MAC) is an experimental agent affecting lipid and carbohydrate metabolism in mammals. The hypocholesterolemic properties of MAC were studied using rats fed on a standard laboratory diet. Because of the insolubility in water, reproducibility of the hypocholesterolemic activity had usually been poor for rats fed ad libitum. The difficulty was overcome by controlled reverse-phase feeding; MAC significantly lowered serum total cholesterol (s-TC) in rats only when given by gastric intubation soon after diet intake.MAC increased fecal excretion of neutral and acidic sterols and also increased biliary flow accompanying increments in biliary cholesterol, bile acids and phospholipids. A much larger increase in neutral sterols was characteristic for MAC. However, intestinal absorption of cholesterol and cholic acid was unaffected by MAC. Three mechanisms therefore seemed to be working in hypocholesterolemic activity: (a) withdrawal of hepatic cholesterol into bile, (b) a larger fecal loss of sterols following increment of biliary sterols and (c) enhanced bile acid synthesis compensating the larger fecal loss. A negative sterol balance often leads to an increase in hepatic cholesterogenesis. However, cholesterogenesis, as judged from incorporation of the precursors, was unchanged by MAC. 相似文献
98.
Susumu Ikegami Yutaka Hirose Yuji Kamiya Saburo Tamura 《Bioscience, biotechnology, and biochemistry》2013,77(13):2453-2457
Partial acid hydrolysis of asterosaponin A, a steroidal saponin, afforded two new disaccharides in addition to O-(6-deoxy-α-d-glucopyranosyl)-(l→4)-6-deoxy-d-glucose which has been characterized in the preceding paper. The formers were demonstrated as O-(6-deoxy-α-d-galactopyranosyl)-(1→4)-6-deoxy-d-glucose and O-(6-deoxy-α-d-galactopyranosyl)-(l→4)-6-deoxy-d-galactose, respectively.Accordingly, the structure of carbohydrate moiety being composed of two moles each of 6-deoxy-d-galactose and 6-deoxy-d-glucose, was established as O-(6-deoxy-α-d-galactopyranosyl)-(l→4)-O-(6-deoxy-α-d-galactopyranosyl)-(l→4)-O-(6-deoxy-α-d-glucopyranosyl)-(l→4)-6-deoxy-d-glucose, which is attached to the steroidal aglycone through an O-acetal glycosidic linkage. 相似文献
99.
100.
Yuji Enomoto Yoshio Furutani Hiroshi Naganawa Masa Hamada Tomio Takeuchi Hamao Umezawa 《Bioscience, biotechnology, and biochemistry》2013,77(7):1331-1336
In the screening for inhibitors of cyclic adenosine-3′,5′-monophosphate phosphodiesterase, two compounds, PDE-I (C13H13N3O5) and PDE-II (C14H14N2O5), were isolated from culture filtrates of a Streptomyces. Concentrations for 50% inhibitions of PDE-I and PDE-II against the high Km enzyme were 15 µm and 13 µm, and those against the low Km enzyme were 65 µm and 130 µm, respectively. Production, isolation and characterization of these compounds are described. 相似文献