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131.
Toshihiro Aoki Ikumi Hyohdoh Noriyuki Furuichi Sawako Ozawa Fumio Watanabe Masayuki Matsushita Masahiro Sakaitani Kazutomo Ori Kenji Takanashi Naoki Harada Yasushi Tomii Mitsuyasu Tabo Kiyoshi Yoshinari Yuko Aoki Nobuo Shimma Hitoshi Iikura 《Bioorganic & medicinal chemistry letters》2013,23(23):6223-6227
Introducing a sulfamide moiety to our coumarin derivatives afforded enhanced Raf/MEK inhibitory activity concomitantly with an acceptable PK profile. Novel sulfamide 17 showed potent HCT116 cell growth inhibition (IC50 = 8 nM) and good PK profile (bioavailability of 51% in mouse), resulting in high in vivo antitumor efficacy in the HCT116 xenograft (ED50 = 4.8 mg/kg). We confirmed the sulfamide moiety showed no negative impact on tests run on the compound to evaluate DMPK (PK profiles in three animal species, CYP inhibition and CYP induction) and the safety profile (hERG and AMES tests). Sulfamide 17 had favorable properties that warranted further preclinical assessment 相似文献
132.
Shuji Yonezawa Hidekuni Yamakawa Chie Muto Motoko Hosono Takahiko Yamamoto Kazunari Hattori Masahiro Sakagami Hiroko Togame Yoshikazu Tanaka Toru Nakano Hiroshi Takemoto Mitsuhiro Arisawa Satoshi Shuto 《Bioorganic & medicinal chemistry letters》2013,23(10):2912-2915
To improve the efficacy of the conformationally restricted BACE1 inhibitors, structural modifications were investigated using two strategies: (a) modification of the terminal aromatic ring and (b) insertion of a spacer between the aromatic rings. In the latter approach, another type of inhibitor 17 bearing an ethylene spacer between two aromatic rings was found to exhibit good BACE1 inhibitory activity, while the corresponding conformationally unrestricted compound 25 showed no activity. This result revealed an interesting effect of a conformational restriction with a cyclopropane ring. 相似文献
133.
Shiro Chihara Akira Ito Masahiro Yahata Takashi Tobita Yasuo Koyama 《Bioscience, biotechnology, and biochemistry》2013,77(12):2709-2717
Eight α-N-acyl colistin nonapeptide derivatives including three aliphatic, four aromatic and one alicyclic derivatives were synthesized by the reaction of colistin nonapeptide with corresponding acid chlorides. This acylation reaction was carried out under the condition kept restrictedly at pH 5,0 in order to introduce an acyl group only to α-amino group but not to γ-amino group existing in a colistin nonapeptide molecule. Synthetic method and several physico-chemical natures of these acyl colistin nonapeptide derivatives are given in this paper.All of the acylated derivatives thus synthesized exhibited characteristic antimicrobial activities. Antimicrobial spectra were substantially based upon a gram-negative type and not so much altered by chemical structures of acyl groups which were considerably differentiated from each other such as cyclic or chain form. Thus, more possible response of carbon size than its structure to the antimicrobial effectiveness was inferred. In spite of almost no toxicity and feeble antimicrobial activity of colistin nonapeptide itself, these acylated colistin nonapeptide derivatives showed a toxicity against mice at a dose of 16.9~70 mg/kg in LD50, which, however, was inferior to the toxicity of colistin sulfate, possibly correspondent to their much weaker antimicrobial activities, as a whole. Hence, it seems likely that acyl part of these acylated colistin nonapeptide derivatives including that of colistin is seriously responsible for the biological activities. 相似文献
134.
Masahiro Fukaya Hajime Okumura Hiroshi Masai Takeshi Uozumi Teruhiko Beppu 《Bioscience, biotechnology, and biochemistry》2013,77(8):2407-2411
A shuttle vector for Gluconobacter suboxydans and Escherichia coli was constructed by ligation of a cryptic plasmid, pMV201, found in G. suboxydans IFO 3130 to E. coli plasmid pACYC177. The chimeric plasmid named pMGlOl carries the ampicillin resistance gene derived from pACYC177 and transforms G. suboxydans var. α IFO 3254 as well as E. coli. The transformation conditions for G. suboxydansvar. α IFO 3254 were examined using pMGlOl DNA. Competent cells were induced efficiently by treatment with LiCl or RbCl CaCl2 which induced the competency of Acetobacter was much less effective. Addition of polyethylene glycol enhanced the transformation efficiency significantly. An efficiency of approximately 102 transformants per μg DNA was finally obtained. 相似文献
135.
Ryo Yamauchi Masahiro Kojima Masatoshi Isogai Koji Kato Yoshimitsu Ueno 《Bioscience, biotechnology, and biochemistry》2013,77(11):2847-2849
The NaCl concentration of the growth medium affected hydrogen production by Lyngbya sp. (No. 108) strain. Cells grown in medium containing 3% NaCl produced the most hydrogen. The carbohydrate content of this strain also increased with increasing NaCl concentration of the growth medium up to 720 fig/mg cells at 5 % NaCl. In the presence of 20 finlol/ml MFA (monofluoroacetic acid), inhibition of hydrogen production was observed. We extracted the glycogen from this nonheterocystous filamentous cyanobacterium, Lyngbya sp. (No. 108), and observed that glycogen and carbohydrate consumption of this strain is coincident with hydrogen production.These results led us to the conclusion that the reserve glycogen or other carbohydrate were used as sources of electron donors for hydrogen production, and that the NaCl concentration of the medium affected the hydrogen production by this strain. 相似文献
136.
The concomitant production of formic acid and pterin compounds from guanosine-5′-triphosphate (GTP) has been found in cell-free extracts of Serratia indica. Among the pterin compounds, l-threo-neopterin–the major Crithidia factor in S. indica–, a cyclic phosphate of neopterin (cNP), d-erythro-neopterin and 6-hydroxymethyl pterin were detected and isolated. Formate-14C elimination from GTP-8-14C was quantitatively distributed in the ethyl acetate layer in the ehyl acetate-hydrochloric acid partition system. Carbon 8 of GTP was released as formic acid. Enzymatic production of formate and cNP was linear for 2 hr at 37°C. Formate production was proportional to the enzyme concentration. The optimum pH for formate elimination was observed around pH 8.6. Optimum temperature for the production of formate and cNP was 50°C. The apparent Km value of GTP for formate production was 6.2×10?bm. Formate eliminating activity was activated by disodium phosphate but was inhibited by Mg2+ or AMP. Incorporation of GTP-U-14C into pterin compounds was also regulated with disodium phosphate. Effective incorporation into cNP and d-erythro-neopterin occurred in the presence of phosphate. When phosphate was omitted from the system, however, effective incorporation into 6-hydroxymethyl pterin was observed. The biosynthetic process of the Crithidia factors, i.e. l-threo-neopterin and cNP, from GTP in S. indica is also discussed. 相似文献
137.
Masahiro Hori Shigeru Sanai Setsuo Takeuchi Akira Kawarada 《Bioscience, biotechnology, and biochemistry》2013,77(8):1693-1700
The seedlings of rice, eggplant and tomato at the 5th leaf stage of growth readily absorbed exogenous 14C-nicotinamide through the root and the foliage in water culture. Within the 24 hr period after the bigining of cultivation, the radioactivity gradually translocated from the part treated with 14C-nicotinamide to the whole plant body. This compound was rapidly metabolised in the plants to at least six metabolites, in which three compounds were identified as nicotinic acid, NAD and NADP. 14C-Nicotinic acid was also taken up quickly through the root of rice and its metabolism showed a similar pattern to that of 14C-nicotinamide. The incorporation of radioactivity into NAD and NADP from 14C-nicotinamide added to cultivating solution at a concentration of 0.21 ppm was decreased to 10~20% by the simultaneous addition of unlabeled nicotinic acid at a concentration about 1000 times higher than that of the labeled one. It was concluded that the biosynthesis of these pyridine nucleotides from nicotinamide was chiefly via nicotinic acid. The formation of 14C-nicotinamide in the 14C-nicotinic acid metabolism suggested a breakdown of NAD. Three unknown compounds observed in both the metabolisms described above were not intermediates in the pyridine nucleotide biosynthesis. 相似文献
138.
139.
Kunisuke Tanaka Toshio Sugimoto Masahiro Ogawa Zenzaburo Kasai 《Bioscience, biotechnology, and biochemistry》2013,77(7):1633-1639
Two types of proteinaceous particles were observed under the electron microscope in the starchy endosperm of rice seeds. One was spherical with lamellar structure (PB-I), while the other was stained homogeneously by osmium tetroxide and not lamellar structured (PB-II). Both types of proteinaceous particles were effectively condensed from the homogenate of developing rice endosperm by an aqueous polymer two-phase system using dextran-DEAE dextran-polyethylene glycol. Separation of both types was carried out by sucrose density gradient centrifugation. These proteinaceous particles were recovered at specific gravities of 1.27 and 1.29 for PB-I and PB-II, respectively. The protein composition of these particles and their solubility fractionation were examined. Prolamin appeared in the PB-I fraction, whereas PB-II was rich in glutelin and globulin. 相似文献
140.