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871.
872.
Asif Ahmed Hyunah Choo Yong Seo Cho Woo-Kyu Park Ae Nim Pae 《Bioorganic & medicinal chemistry》2009,17(13):4559-4568
Pharmacophore modelling, docking and virtual screening have become important tool in drug discovery process. Serotonin 2C (5-HT2C) receptor ligands have got major attention for their therapeutic uses as antidepressant and anorectic agents. Two step pharmacophore and docking based virtual screening was done using 5-HT2C agonists. Two common feature pharmacophore directed virtual hits had submicromolar activity. Refined pharmacophore with excluded volumes was constructed and combined with homology model based docking. Best hit from this virtual screening showed IC50 of 20.1 nM. Similarity search of this hit compound resulted more active ligand with 7.8 nM activity. 相似文献
873.
A wheat (Triticum aestivum L., near isogenic line of Hamlet) O-methyltransferase (OMT) was previously reported as a putative caffeic acid OMT (TaCOMT1), involved in lignin biosynthesis, based on its high sequence similarity with a number of graminaceous COMTs. The fact that the putative TaCOMT1 exhibits a significantly high sequence homology to another recently characterized wheat flavone-specific OMT (TaOMT2), and that molecular modeling studies indicated several conserved amino acid residues involved in substrate binding and catalysis of both proteins, prompted an investigation of its appropriate substrate specificity. We report here that TaCOMT1 exhibits highest preference for the flavone tricetin, and lowest activity with the lignin precursors, caffeic acid/5-hydroxyferulic acid as the methyl acceptor molecules, indicating that it is not involved in lignin biosynthesis. We recommend its reannotation to a flavone-specific TaOMT1 that is distinct from TaOMT2. 相似文献
874.
875.
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877.
Ji-Won Lee Jae-Yong Ahn Shin-ichi Hasegawa Byung-Yoon Cha Takayuki Yonezawa Kazuo Nagai Hwa-Jeong Seo Won-Bae Jeon Je-Tae Woo 《Cytotechnology》2009,61(3):125-134
Osteoclasts are multinucleated cells that play a crucial role in bone resorption, and are formed by the fusion of mononuclear
osteoclasts derived from osteoclast precursors of the macrophage lineage. Compounds that specifically target functional osteoclasts
would be ideal candidates for anti-resorptive agents for clinical applications. In the present study, we investigated the
effects of luteolin, a flavonoid, on the regulation of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis,
functions and signaling pathway. Addition of luteolin to a coculture system of mouse bone marrow cells and ST2 cells in the
presence of 10−8 M 1α,25(OH)2D3 caused significant inhibition of osteoclastogenesis. Luteolin had no effects on the 1α,25(OH)2D3-induced expressions of RANKL, osteoprotegerin and macrophage colony-stimulating factor mRNAs. Next, we examined the direct
effects of luteolin on osteoclast precursors using bone marrow macrophages and RAW264.7 cells. Luteolin completely inhibited
RANKL-induced osteoclast formation. Moreover, luteolin inhibited the bone resorption by mature osteoclasts accompanied by
the disruption of their actin rings, and these effects were reversely induced by the disruption of the actin rings in mature
osteoclasts. Finally, we found that luteolin inhibited RANKL-induced osteoclastogenesis through the suppression of ATF2, downstream
of p38 MAPK and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) expression, respectively.
Taken together, the present results indicate that naturally occurring luteolin has inhibitory activities toward both osteoclast
differentiation and functions through inhibition of RANKL-induced signaling pathway as well as actin ring disruption, respectively. 相似文献
878.
Joong-Sun Kim Myoung-Sub Song Heung-Sik Seo Miyoung Yang Sung-Ho Kim Jong Choon Kim Heechul Kim Toru R. Saito Taekyun Shin Changjong Moon 《Histochemistry and cell biology》2009,131(4):501-507
Basal activity and cellular localization of cAMP response element-binding protein (CREB) was examined in mouse testis during
postnatal development and spermatogenesis. Testes of ICR mice sampled on postnatal day (PND) 3, 7, 14, 21, 28, 35, 42, and
49 were analyzed using Western blotting. Basal CREB activity was significantly higher in early phase (PND 3–7) developing
testes than in intermediate- and late-phase developing (PND 14–42) and adult testes (PND 49). Furthermore, immunohistochemical
analysis demonstrated the change of CREB phosphorylation in various testicular cell types during postnatal development. In
particular, CREB phosphorylation in seminiferous tubules of the adult testis varied according to the spermatogenic cycle,
while phosphorylation was evident in spermatogonia during all stages. Phosphorylation was moderate in pachytene spermatocytes
of stages I–III and intense in round and elongate spermatids of spermiogenesis in stages XII–IX. These results suggest that
CREB plays an important role in cell proliferation and differentiation in the early phase of postnatal development and spermatogenesis
of mouse testis. 相似文献
879.
Guanosine 5’-diphosphate (GDP)-l-fucose, an activated form of a nucleotide sugar, plays an important role in a wide range of biological functions. In this study, the enhancement of GDP-l-fucose production was attempted by supplementation of mannose, which is a potentially better carbon source to be converted into GDP-l-fucose than glucose, and combinatorial overexpression of the genes involved in the biosynthesis of GDP-d-mannose, a precursor of GDP-l-fucose. Supply of a mannose and glucose led to a 1.3-fold-increase in GDP-l-fucose concentration (52.5 ± 0.8 mg l?1) in a fed-batch fermentation of recombinant E. coli BL21star(DE3) overexpressing the gmd and wcaG genes, compared with the case using glucose as a sole carbon source. A maximum GDP-l-fucose concentration of 170.3 ± 2.3 mg l?1, corresponding to a 4.4-fold enhancement compared with the control strain overexpressing gmd and wcaG genes only, was achieved in a glucose-limited fed-batch fermentation of a recombinant E. coli BL21star(DE3) strain overexpressing manB, manC, gmd and wcaG genes. Further improvement of GDP-l-fucose production was not obtained by additional overexpression of the manA gene. 相似文献
880.
Jong Yup Kim Hee Jeong Seo Sung-Han Lee Myung Eun Jung Kwangwoo Ahn Jeongmin Kim Jinhwa Lee 《Bioorganic & medicinal chemistry letters》2009,19(1):142-145
Since the CB1 receptor antagonist SR141716 (rimonabant) was reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target in the treatment of obesity. Several series of derivatives based on diarylimidazolyl oxadiazole and thiadiazole scaffolds were synthesized and tested for CB1 receptor binding affinity. SAR studies directed toward the optimization of imidazole scaffolds resulted in the discovery of 10s which showed highest potency for CB1 receptor binding affinity (IC50 = 1.91 nM) prepared to date. 相似文献