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991.
Tanabe G Yoshikai K Hatanaka T Yamamoto M Shao Y Minematsu T Muraoka O Wang T Matsuda H Yoshikawa M 《Bioorganic & medicinal chemistry》2007,15(11):3926-3937
De-O-sulfonated analogs (10a, Y(-)=CH(3)OSO(3) and 10b, Y(-)=Cl) of salacinol, a naturally occurring glycosidase inhibitor, and its diastereomer (12a, Y(-)=CH(3)OSO(3)) with L-thiosugar moiety (1,4-dideoxy-1,4-epithio-L-arabinitol) were prepared. Their inhibitory activities against intestinal maltase and sucrase were examined and compared with those of the parent alpha-glycosidase inhibitor, salacinol (1a). Compounds 10a and 10b showed a potent inhibitory activity equal to that of 1a against both enzymes, although 12a was a weak inhibitor against sucrase and maltase. These results indicated that the O-sulfonate anion moiety of 1a is not essential for the inhibitory activity. 相似文献
992.
Kobayashi E Shimazaki M Miyamoto Y Masuno H Yamamoto K DeLuca HF Yamada S Shimizu M 《Bioorganic & medicinal chemistry》2007,15(3):1475-1482
We have synthesized four new geometric isomers of 1alpha,25-dihydroxy-2-(2'-fluoroethylidene)-19-norvitamin D analogs 1 and 2 having a 20R- and 20S-configuration, whose structures are correlated with 2MD possessing high potencies in stimulating bone formation in vitro and in vivo. The E-isomers of (20R)- and (20S)-2-fluoroethylidene analogs 1a and 1b were comparable with the natural hormone 1alpha,25-(OH)(2)D(3) in binding to the vitamin D receptor (VDR), while two Z-isomers 2a and 2b were about 15-20 times less active than the hormone. In inducing expression of the vitamin D responsive element-based luciferase reporter gene, the E-isomers 1a and 1b were 1.2- and 8.6-fold more potent than the hormone, respectively, while the Z-isomers 2a and 2b had 27-55% of the potency. On the basis of the biological activities and a docking simulation based on X-ray crystallographic analysis of the VDR ligand-binding pocket, the structure-activity relationships of the fluorinated 19-norvitamin D analogs are discussed. 相似文献
993.
Ali HI Tomita K Akaho E Kambara H Miura S Hayakawa H Ashida N Kawashima Y Yamagishi T Ikeya H Yoneda F Nagamatsu T 《Bioorganic & medicinal chemistry》2007,15(1):242-256
Novel 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides were prepared as a new class of antitumor agents and showed significant antitumor activities against NCI-H 460, HCT 116, A 431, CCRF-HSB-2, andKB cell lines. In vivo investigation, 2-deoxo-10-methyl-2-phenyl-5-deazaflavin exhibited the effective antitumor activity against A 431 human adenocarcinoma cells transplanted subcutaneously into nude mouse. Furthermore, AutoDock study has been done by binding of the flavin analogs into PTK pp60(c-src), where a good correlation between their IC(50) and AutoDock binding free energy was exhibited. In particular, 2-deoxo-2-phenylflavin-5-oxides exhibited the highest potential binding affinity within the binding pocket of PTK. 相似文献
994.
A simple and rapid continuous-flow immunosensor based on surface plasmon resonance (SPR) has been developed for detection of insulin as low as 1 ng ml-1 (ppb) with a response time of less than 5 min. At first, a heterobifunctional oligo(ethyleneglycol)-dithiocarboxylic acid derivative (OEG-DCA) containing dithiol and carboxyl end groups was used to functionalize the thin Au-film of SPR chip. Insulin was covalently bound to the Au-thiolate monolayer of OEG-DCA for activating the sensor surface to immunoaffinity interactions. An on-line competitive immunosensing principle is examined for detection of insulin, in which the direct affinity binding of anti-insulin antibody to the insulin on sensor surface is examined in the presence and absence of various concentrations of insulin. Immunoreaction of anti-insulin antibody with the sensor surface was optimized with reference to antibody concentration, sample analysis time and flow-rate to provide the desired detection limit and determination range. With the immunosensor developed, the lowest detectable concentration of insulin is 1 ng ml-1 and the determination range covers a wide concentration of 1-300 ng ml-1. The developed OEG-monolayer based sensor chip exhibited high resistance to non-specific adsorption of proteins, and an uninterrupted highly sensitive detection of insulin from insulin-impregnated serum samples has been demonstrated. After an immunoreaction cycle, active sensor surface was regenerated simply by a brief flow of an acidic buffer (glycine.HCl; pH 2.0) for less than 1 min. A same sensor chip was found reusable for more than 25 cycles without an appreciable change in the original sensor activity. 相似文献
995.
Saijo R Tsunekawa S Murakami H Shirai N Ikeda S Odashima K 《Bioorganic & medicinal chemistry letters》2007,17(3):767-771
New ditopic sensory elements 2 and 3 for catecholamines based on a hexahomotrioxacalix[3]arene, with a boronic acid substituent appended, were designed and synthesized. As an interesting mode of molecular recognition at membrane surfaces, the host, when incorporated into poly(vinyl chloride) (PVC) liquid membranes, displayed excellent potentiometric selectivity for dopamine over other catecholamines (noradrenaline and adrenaline) and inorganic cations (Na+, K+, and NH4+). 相似文献
996.
The methanol extract of Sophora flavescens, which is used in traditional Chinese medicine (sophorae radix), showed potent Na(+)-glucose cotransporter (SGLT) inhibitory activity. Our search for active components identified many well-known flavonoid antioxidants: kurarinone, sophoraflavanone G, kushenol K, and kushenol N. 相似文献
997.
Komatsu T Hirano T Songkram C Kawachi E Kagechika H 《Bioorganic & medicinal chemistry》2007,15(9):3115-3126
Thyroid hormones play important roles in growth, development and homeostasis, and disruption of their functions induces serious disease, so novel synthetic thyroid hormone analogues are candidates for clinical application. We designed and synthesized novel diphenylamine derivatives with a thiazolidinedione moiety as the terminal polar group as thyroid hormone receptor (TR) antagonists. Compounds bearing an appropriately sized N-alkyl group showed antagonistic activities towards both the hTRalpha1 and hTRbeta1 subtypes. 相似文献
998.
999.
Oba M Fukushima S Kanayama N Aoyagi K Nishiyama N Koyama H Kataoka K 《Bioconjugate chemistry》2007,18(5):1415-1423
A cyclic RGD peptide-conjugated block copolymer, cyclo[RGDfK(CX-)]-poly(ethylene glycol)-polylysine (c(RGDfK)-PEG-PLys), was synthesized from acetal-PEG-PLys under mild acidic conditions and spontaneously associated with plasmid DNA (pDNA) to form a polyplex micelle in aqueous solution. The cyclic RGD peptide recognizes alphavbeta3 and alphavbeta5 integrin receptors, which play a pivotal role in angiogenesis, vascular intima thickening, and the proliferation of malignant tumors. The c(RGDfK)-PEG-PLys/pDNA polyplex micelle showed a remarkably increased transfection efficiency (TE) compared to the PEG-PLys/pDNA polyplex micelle for the cultured HeLa cells possessing alphavbeta3 and alphavbeta5 integrins. On the other hand, in the transfection against the 293T cells possessing no alphavbeta3 and a few alphavbeta5 integrins, the TE of the c(RGDfK)-PEG-PLys/pDNA micelle showed no increase compared to the TE of the PEG-PLys/pDNA micelle. Flow cytometric analysis revealed a higher uptake of the c(RGDfK)-PEG-PLys/pDNA micelle than the PEG-PLys/pDNA micelle against HeLa cells, consistent with the transfection results. Furthermore, a confocal laser scanning microscopic observation revealed that the pDNA in the c(RGDfK)-PEG-PLys micelle preferentially accumulated in the perinuclear region of the HeLa cells within 3 h of incubation. No such fast and directed accumulation of pDNA to the perinuclear region was observed for the micelles without c(RGDfK) ligands. These results indicate that the increase in the TE induced by the introduction of the c(RGDfK) peptide ligand was due to an increase in cellular uptake as well as facilitated intracellular trafficking of micelles toward the perinuclear region via alphavbeta3 and alphavbeta5 integrin receptor-mediated endocytosis, suggesting that the cyclic RGD peptide-conjugated polyplex micelle has promising feasibility as a site-specifically targetable gene delivery system. 相似文献
1000.