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101.
Yoshiyuki Sato Yu Onozaki Tetsuya Sugimoto Hideki Kurihara Kaori Kamijo Chie Kadowaki Toshiaki Tsujino Akiko Watanabe Sachie Otsuki Morihiro Mitsuya Masato Iida Kyosuke Haze Takumitsu Machida Yoko Nakatsuru Hideya Komatani Hidehito Kotani Yoshikazu Iwasawa 《Bioorganic & medicinal chemistry letters》2009,19(16):4673-4678
A novel class of imidazopyridine derivatives was designed as PLK1 inhibitors. Extensive SAR studies supported by molecular modeling afforded a highly potent and selective compound 36. Compound 36 demonstrated good antitumor efficacy in xenograft nude rat model. 相似文献
102.
Jun Ohwada Sawako Ozawa Masami Kohchi Hiroshi Fukuda Chikako Murasaki Hitomi Suda Takeshi Murata Satoshi Niizuma Masao Tsukazaki Kazutomo Ori Kiyoshi Yoshinari Yoshiko Itezono Mika Endo Masako Ura Hiromi Tanimura Yoko Miyazaki Akira Kawashima Shunsuke Nagao Eitarou Namba Koutarou Ogawa Nobuo Shimma 《Bioorganic & medicinal chemistry letters》2009,19(10):2772-2776
CH0793076 (1) is a novel hexacyclic camptothecin analog showing potent antitumor activity in various human caner xenograft models. To improve the water solubility of 1, water-soluble prodrugs were designed to generate an active drug 1 nonenzymatically, thus expected to show less interpatient PK variability than CPT-11. Among the prodrugs synthesized, 4c (TP300, hydrochloride) having a glycylsarcosyl ester at the C-20 position of 1 is highly water-soluble (>10 mg/ml), stable below pH 4 and rapidly generates 1 at physiological pH in vitro. The rapid (ca. <1 min) generation of 1 after incubation of TP300 with plasma (mouse, rat, dog and monkey) was also demonstrated. TP300 showed a broader antitumor spectrum and more potent antitumor activity than CPT-11 in various human cancer xenograft models. 相似文献
103.
Burki Rajendar Arivazhagan Rajendran Yusuke Sato Seiichi Nishizawa Norio Teramae 《Bioorganic & medicinal chemistry》2009,17(1):351-359
Isoxanthopterin (IX) has two edges with hydrogen bond-forming sites suitable for binding to thymine (T) and cytosine (C). The binding affinity of IX for T or C is stronger than for adenine (A) and guanine (G), whereas the base selectivity of IX for T over C (and vice versa) is moderate. In order to improve both the binding affinity and base selectivity for T over C or C over T, a methyl group is introduced respectively at the N-3 or N-8 position of IX. This leads to the known ligands 3-methyl isoxanthopterin (3-MIX) and 8-methyl isoxanthopterin (8-MIX), and the binding affinity for C or T is expected to be tuned and improved by methyl substitution. Indeed, 3-MIX selectively binds to T more strongly than IX with a binding constant of 1.5 × 106 M?1 and it loses its binding affinity for C. In contrast, 8-MIX selectively binds to C over T with a binding constant of 1.0 × 106 M?1 and the binding affinity is greatly improved compared to the parent ligand IX. The thermodynamics of the ligand–nucleotide interaction is analyzed by isothermal calorimetric titrations, and the results show that the interaction follows a 1:1 stoichiometry and is enthalpy-driven. The introduction of methyl groups at both N-3 and N-8 positions results in an increase in enthalpy of the ligand–nucleotide interaction, which leads to the improved binding affinity. 相似文献
104.
Muhammad Shahbaz Akhtar Yoko Oki Tadashi Adachi 《Acta Botanica Sinica》2009,(11):1024-1039
Non-mycorrhizal Brassica does not produce specialized root structures such as cluster or dauciform roots but is an effective user of P compared with other crops. In addition to P-uptake, utilization and remobilization activity, acquisition of orthophosphate (Pi) from extracellular sparingly P-sources or unavailable bound P-forms can be enhanced by biochemical rescue mechanisms such copious H+-efflux and/or carboxylates exudation into rhizosphere by roots via plasmalemma H+ ATPase and anion channels triggered by P-starvation. To visualize the dissolution of sparingly soluble Ca-phosphate (Ca-P), newly formed Ca-P was suspended in agar containing other essential nutrients. With NH4+ applied as the N source, the precipitate dissolved in the root vicinity can be ascribed to rhizosphere acidification, whereas no dissolution occurred with nitrate nutrition. To observe in situ rhizospheric pH changes, images were recorded after embedding the roots in agar containing bromocresol purple as a pH indicator. P-tolerant cultivar showed a greater decrease in pH than the sensitive cultivar in the culture media (the appearance of typical patterns of various colors of pH indicator in the root vicinity), and at stress P-level this acidification was more prominent. In experiment 2, low P-tolerant class-I cultivars (Oscar and Con-II) showed a greater decrease in solution media pH than low P-sensitive class-II (Gold Rush and RL-18) cultivars, and P-contents of the cultivars was inversely related to decrease in culture media pH. To elucidate P-stress- induced remodeling and redesigning in a root architectural system, cultivars were grown in rhizoboxes in experiment 3. The elongation rates of primary roots increased as P-supply increased, but the elongation rates of the branched zones of primary roots decreased. The length of the lateral roots and topological index values increased when cultivars were exposed to a P-stress environment. To elucidate Pi-uptake kinetics, parameters related to P influx: maximal 相似文献
105.
Muhammad Shahbaz Akhtar Yoko Oki Tadashi Adachi 《Acta Botanica Sinica》2009,(11):1008-1023
Phosphorus (P) starvation is highly notorious for limiting plant growth around the globe. To combat P-starvation, plants constantly sense the changes in their environment, and elicit an elegant myriad of plastic responses and rescue strategies to enhance P-solublization and acquisition from bound soil P-forms. Relative growth responses, P-solublization and P- acquisition ability of 14 diverse Brassica cultivars grown with sparingly soluble P-sources (Rock-P (RP) and Ca3(PO4)2 (TCP)) were evaluated in a solution culture experiment. Cultivars showed considerable genetic diversity in terms of biomass accumulation, concentration and contents of P and Ca in shoots and roots, P-stress factor (PSF) and P use efficiency. Cultivars showed variable P-stress tolerance, and cultivars depicting low PSF and high P-efficiency values were better adaptable to P-starvation. In experiment 2, after initial feeding on optimum nutrition for 12 d after transplanting (DAT), class-I (low P-tolerant (Oscar and Con-II)) and class-II (low P-sensitive (Gold Rush and RL-18)) cultivars were exposed to P-free environment for 25 d. All of the cultivars remobilized P from above ground parts to their roots during growth in P-free environment, the magnitude of which was variable in tested cultivars. P-concentrations ([P]s) at 37 DAT were higher in developing compared with developed leaves. Translocation of absorbed P from metabolically inactive to active sites in P- stressed plants may have helped class-I cultivars to establish a better rooting system, which provided a basis for enhanced P-utilization efficiency (PUE) and tolerance against P-stress. By supplying TCP and RP spatially separated from other nutrients in split root study, class-I cultivars were still able to mobilize RP and TCP more efficiently compared with class-II cultivars. To compare the growth behavior under P-stress, cultivars were grown in pots for 41 d after sowing, using a soil low in P (NaHCO3-extractable P = 3.97 mg/kg, M 相似文献
106.
107.
Yutaka Horiuchi Makiko Tominaga Mika Ichikawa Masao Yamashita Yuri Jikumaru Yoko Nariai Yuko Nakajima Masato Kuwabara Masayoshi Yukawa 《Microbiology and immunology》2009,53(8):468-474
It is well known that lymphocytes from patients with advanced-stage cancer have impaired immune responsiveness and that type1 T lymphocyte subsets in tumor bearing hosts are suppressed. Treg have been reported to comprise a subgroup which inhibits T cell mediated immune responses. In the present study, the percentage of Treg, Th1 and Tc1 in the peripheral blood of tumor bearing dogs with or without metastases was evaluated. The percentages of Th1 and Tc1 in dogs with metastatic tumor were significantly less, and that of Treg was significantly greater, than those of dogs without metastatic tumor. The percentage of Treg showed an inverse correlation with that of Th1 and Tc1 in tumor bearing dogs. It was concluded that an increase in Treg in the peripheral blood of dogs with metastatic tumor may induce suppression of tumor surveillance by the Type1 immune response and lead to metastasis of tumor[0][0].[0] 相似文献
108.
Yoko Nishikawa 《Plant Ecology》2009,202(2):337-347
I studied the relationship between seed-set patterns within inflorescences and temporal variations in light and pollinator
availabilities for 2 years in the spring ephemeral species Gagea lutea in a deciduous forest. Timing of canopy closure and seasonal trend of pollinator frequency did not synchronize with the annual
fluctuation in flowering phenology. In the early snowmelt year, seed-set success reflected the seasonal pollinator abundance
from early to middle flowering periods. In the late snowmelt year, however, seed-set rates were independent of pollinator
activity and decreased with canopy closing even after hand pollination. The restricted seed production by defoliation and
the increase in seed-set rates at the forest edge suggested that seed production was supported by current photosynthetic carbon
gain. Thus, annual fluctuations of reproductive success can explain the variation in flowering phenology within a population
although seasonal light deterioration would serve as a selective force for flowering in the early season. 相似文献
109.
Michio Hashimoto Hossain Md Shahdat Masanori Katakura Yoko Tanabe Shuji Gamoh Koji Miwa Toshio Shimada Osamu Shido 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2009,1791(4):289-296
Amyloid β peptide25–35 (Aβ25–35) encompasses one of the neurotoxic domains of full length Aβ1–40/42, the major proteinaceous component of amyloid deposits in Alzheimer's disease (AD). We investigated the effect of docosahexaenoic acid (DHA, 22:6, n-3), an essential brain polyunsaturated fatty acid, on the in vitro fibrillation of Aβ25–35 and found that it significantly reduced the degree of fibrillation, as shown by a decrease in the intensity of both the thioflavin T and green fluorescence in confocal microscopy. Transmission electron microscopy revealed that DHA-incubated samples were virtually devoid of structured fibrils but had an amorphous-like consistency, whereas the controls contained structured fibers of various widths and lengths. The in vitro fibrillation of Aβ25–35 appeared to be pH-dependent, with the strongest effect seen at pH 5.0. DHA inhibited fibrillation at all pHs, with the strongest effect at pH 7.4. It also significantly decreased the levels of Aβ25–35 oligomers. Nonreductive gradient gel electrophoresis revealed that the molecular size of the oligomers of Aβ25–35 was 10 kDa (equivalent to decamers of Aβ25–35) and that DHA dose-dependently reduced these decamers. These results suggest that DHA decreases the in vitro fibrillation of Aβ25–35 by inhibiting the oligomeric amyloid species and, therefore, Aβ25–35-related neurotoxicity or behavioral impairment could be restrained by DHA. 相似文献
110.