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101.
Ryunosuke Yoshino Nobuaki Yasuo Daniel Ken Inaoka Yohsuke Hagiwara Kazuki Ohno Masaya Orita Masayuki Inoue Tomoo Shiba Shigeharu Harada Teruki Honma Emmanuel Oluwadare Balogun Josmar Rodrigues da Rocha Carlos Alberto Montanari Kiyoshi Kita Masakazu Sekijima 《PloS one》2015,10(5)
BackgroundChagas disease, caused by the parasite Trypanosoma cruzi, is a neglected tropical disease that causes severe human health problems. To develop a new chemotherapeutic agent for the treatment of Chagas disease, we predicted a pharmacophore model for T. cruzi dihydroorotate dehydrogenase (TcDHODH) by fragment molecular orbital (FMO) calculation for orotate, oxonate, and 43 orotate derivatives.Conclusions/SignificanceFMO-based interaction energy analyses revealed a pharmacophore model for TcDHODH inhibitor. Hydrogen bond acceptor pharmacophores correspond to Lys43 and Lys214, hydrogen bond donor and acceptor pharmacophores correspond to Asn67 and Asn194, and the aromatic ring pharmacophore corresponds to FMN, which shows important characteristics of compounds that inhibit TcDHODH. In addition, the Lys214 residue is not conserved between TcDHODH and human DHODH. Our analysis suggests that these orotate derivatives should preferentially bind to TcDHODH, increasing their selectivity. Our results obtained by pharmacophore modeling provides insight into the structural requirements for the design of TcDHODH inhibitors and their development as new anti-Chagas drugs. 相似文献
102.
103.
A total of 10 steroidal glycosides, together with three new spirostanol glycosides (6-8), a new furostanol glycoside (9), and a new cholestane glycoside (10), were isolated from the rhizomes of Clintonia udensis (Liliaceae). The structures of the new compounds were determined on the basis of extensive spectroscopic analyses, including 2-D nuclear magnetic resonance (NMR) data, and of hydrolytic cleavage followed by chromatographic or spectroscopic analyses. The isolated glycosides were evaluated for their cytotoxic activity against HL-60 leukemia cells. Spirostanol glycosides 1 and 2, and furostanol glycoside 4 showed cytotoxic activity with IC(50) values of 3.2+/-0.02, 2.2+/-0.12, and 2.2+/-0.06 microg/ml, respectively. Neither the spirostanol and furostanol saponins with a hydroxy group at C-1 (6 and 9) and C-12 (7 and 8) nor cholestane glycosides (5 and 10) exhibited apparent cytotoxic activity at a sample concentration of 10 microg/ml. 相似文献
104.
Horibe T Yosho C Okada S Tsukamoto M Nagai H Hagiwara Y Tujimoto Y Kikuchi M 《Journal of biochemistry》2002,132(3):401-407
To elucidate the function of protein disulfide isomerase (PDI), we screened for PDI-binding proteins in a bovine liver extract using affinity column chromatography. One of the binding proteins was identified by SDS-PAGE and N-terminal amino acid sequence analysis to be cyclophilin B (Cyp B). Use of the BIACORE system revealed that purified bovine Cyp B bound specifically to bovine PDI with a K(D) value of 1.19 x 10(-5) M. Interestingly, the binding affinity between PDI and Cyp B was strengthened by preincubation of the Cyp B with cyclosporin A (CsA), yielding a K(D) value of 3.67 x 10(-6) M. Although the interaction between PDI and Cyp B affected neither the isomerase activity of PDI nor the peptidyl-prolyl cis-trans isomerase activity of Cyp B, Cyp B increased the chaperone activity of PDI. However, the complex of Cyp B and CsA completely inhibited the chaperone activity of PDI. Thus, PDI and Cyp B appear to cooperate with each other to regulate the functional expression of proteins in vivo. 相似文献
105.
106.
Tatsuya Kamima Yoshihiro Ueda Jun-ichi Fukunaga Mikoto Tamura Yumiko Shimizu Yuta Muraki Yasuo Yoshioka Nozomi Kitamura Yuya Nitta Masakazu Otsuka Hajime Monzen 《Reports of Practical Oncology and Radiotherapy》2021,26(6):849
BackgroundThe aim of this study was to investigate the performance of the RapidPlan (RP ) using models registered pseudostructures, and to determine how many structures are required for automatic optimization of volumetric modulated arc therapy (VMAT) for postoperative uterine cervical cancer.Materials and methodsPseudo-structures around the PTV were retrospectively contoured for patients who had completed treatment at five institutions. For 22 common patients, plans were generated with a single optimization for models with two (RP_2), four (RP_4), and five (RP_5) registered structures, and the dosimetric parameters of these models were compared with a clinical plan with several optimizations.ResultsMost dosimetric parameters showed no major differences between each RP model. In particular, the rectum Dmax, V50Gy, and V40Gy with RP_2, RP_4, and RP_5 were not significantly different, and were lower than those of the clinical plan. The average proportions of plans achieving acceptable criteria for dosimetric parameters were close to 100% for all models. Using RP_2, the average time for the VMAT planning was reduced by 88 minutes compared with the clinical plan.ConclusionThe RapidPlan model with two registered pseudo-structures could generate clinically acceptable plans while saving time. 相似文献
107.
Relation between fatty acid composition of cellular phospholipids and the excretion of L-glutamic acid was investigated using Corynebacterium alkanolyticum GL–21 (a glycerol auxotroph).When grown on n-hexadecane, the proportion of unsaturated fatty acids was higher in L-glutamic acid-accumulating cells than in L-glutamic acid-nonaccumulating cells. When grown on fructose or acetic acid, the reverse relation was observed. Moreover, cells containing no oleic acid produced L-glutamic acid from n-pentadecane.These results suggest that the membrane permeability to L-glutamic acid is not always controlled by the cellular content of unsaturated fatty acids. 相似文献
108.
Amada H Sekiguchi Y Ono N Matsunaga Y Koami T Asanuma H Shiozawa F Endo M Ikeda A Aoki M Fujimoto N Wada R Sato M 《Bioorganic & medicinal chemistry letters》2012,22(5):2024-2029
A novel series of 4-thiazolylimidazoles was synthesized as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-β-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. N-{[5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-2-yl]methyl}butanamide 20, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC(50)=8.2nM) as well as inhibitory activity against TGF-β-induced Smad2/3 phosphorylation at a cellular level (IC(50)=32nM). 相似文献
109.
110.
Takahiro Honda Takahiro Terao Hiroyuki Aono Masakazu Ban 《Bioorganic & medicinal chemistry》2009,17(2):699-708
We designed and synthesized a novel 1,4-benzoxazin-3-one derivative 4 which would have inhibitory activities against tyrosine kinases. They could be synthesized easily from various carboxylic acids 10 and commercially available amines using TFP resin without purification. In this article, we will report the design and synthesis of a novel 1,4-benzoxazin-3-one chemical library 4 and the inhibitory activities against KDR and ABL which are closely related to chronic diseases such as cancer. 相似文献