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971.
《Journal of receptor and signal transduction research》2013,33(1):37-40
AbstractInsulin plays an important role in various metabolic as well as anabolic actions in cells, including osteoblast cells. In the present study, we explored to determine if insulin receptor could associate with syndecan-1 in response to insulin and such association could lead to the activation of subsequent ERK I/II and alkaline phosphatase (ALP) in osteoblast cells. Insulin rapidly induces the association of insulin receptor with syndecan-1. Synstatin is a specific peptide inhibitor that blocks the binding of syndecan-1 to integrate. In the presence of synstatin, insulin-stimulated ERK I/II activation was dramatically inhibited, suggesting that syndecan-1/integrin interaction is essential in the activation of ERK I/II by insulin. Pretreatment of synstatin also inhibited the insulin-stimulated ALP activity. Taken together, these results suggest that insulin stimulates the association of insulin receptor with syndecan-1 and the complex formation of syndecan-1 and integrin could play an important role in ERK I/II–ALP signaling pathway in osteoblast cells. 相似文献
972.
973.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):427-442
AbstractPyrazoles, categorized as nitrogen-containing heterocycles, are well known for their interminable participation in the field of perpetual research and development of therapeutical active agents. As a consequence pyrazoles became an inevitable core of numerous drugs having diverse activities. The broad spectrum of activities portrayed by the pyrazoles instigated the researchers to modify the pyrazole ring as 4,5-dihydro-1H-pyrazoles commonly known as 2-pyrazolines. The present review is a concerted effort to retrace compounds covered from 2009-till date which owe diverse biological activities to the 2-pyrazoline scaffold and also condenses the retro-synthetic approaches employed for their synthesis. This endeavor culminated in revelation that inhibitory potential varied when the substituents in particular N-substituents of 2-pyrazolines were altered. 相似文献
974.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):312-317
The plasma membrane H+-ATPase pump (Pma1p) has been proposed as a viable target for antifungal drugs since this high capacity proton pump plays a critical role in the intracellular regulation of pH and in nutrient uptake of yeast and other fungi. In recent years, this and other laboratories have verified that the antifungal activity of 2-phenylbenzisoselenazol-3(2H)-one, an organoselenium compound commonly referred to as ebselen (1), stems, at least in part, from its inhibitory action on the fungal Pma1p. In the present study, the antifungal efficacy of 2-(3-pyridinyl)-benzisoselenazol-3(2H)-one (2) and 2-phenylbenzisoselenazol-3(2H)-one 1-oxide (3), two ebselen analogs, was evaluated using a strain of S. cerevisiae and compared against that of 1. In addition, the study also examined the inhibitory potential of these three compounds toward the Pma1p of S. cerevisiae. Based on mean IC50 values, the antifungal potency was found to decrease in the order 3?>?1?>?2. However, in terms of inhibitory action on Pma1p, the potency decreased in the order 1?>?3?>?2. The magnitude of these activities appears to be correlated with the corresponding log P values, with compound 2 being the most hydrophilic and the least active of the three. 相似文献
975.
Talia Fuchs Julian N. Trollor John Crawford David A. Brown Bernhard T. Baune Katherine Samaras Lesley Campbell Samuel N. Breit Henry Brodaty Perminder Sachdev Evelyn Smith 《Aging cell》2013,12(5):882-889
Higher levels of macrophage inhibitory cytokine‐1, also known as growth differentiation factor 15 (MIC‐1/GDF15), are associated with adverse health outcomes and all‐cause mortality. The aim of this study was to examine the relationships between MIC‐1/GDF15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment (MCI), at baseline (Wave 1) and prospectively at 2 years (Wave 2), in nondemented participants aged 70–90 years. Analyses were controlled for age, sex, education, Framingham risk score, history of cerebrovascular accident, acute myocardial infarction, angina, cancer, depression, C‐reactive protein, tumor necrosis factor‐α, interleukins 6 and 12, and apolipoprotein ε4 genotype. Higher MIC‐1/GDF15 levels were significantly associated with lower global cognition at both waves. Cross‐sectional associations were found between MIC‐1/GDF15 and all cognitive domains in Wave 1 (all P < 0.001) and between processing speed, memory, and executive function in Wave 2 (all P < 0.001). Only a trend was found for the prospective analyses, individuals with high MIC‐1/GDF15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC‐1/GDF15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in Wave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics (ROC) analysis was used to determine MIC‐1/GDF15 cutoff values associated with cognitive decline and showed that a MIC‐1/GDF15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC‐1/GDF15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship. 相似文献
976.
Gerhard Müller Markus Albers Gerhard He?ler? Thomas E. Lehmann Hiromi Okigami Masaomi Tajimi 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):309-312
Terephthalic acid based derivatives containing β- and γ-amino acid residues were prepared as antagonists of the leukocyte cell adhesion process that is mediated through the interaction of the very late antigen 4 (VLA-4) and the vascular cell adhesion molecule 1 (VCAM-1). The compounds 2, 10–12, 14, and 16–17 inhibited the adhesion in a cell based assay in the low and sub micromolar range. 相似文献
977.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):1199-1204
A series of 5,7-dihydroxyflavanone derivatives were synthesized and identified as reversible and competitive protein tyrosine phosphatase (PTP) 1B inhibitors with IC50 values in the micromolar range. Compound 4k had the most potent in vitro inhibition activity against PTP1B (IC50 = 2.37?±?0.37 μM) and the greatest selectivity (3.7-fold) for PTP1B relative to T-cell protein tyrosine phosphatase. Cell-based studies revealed that 4k was membrane-permeable and enhanced insulin receptor tyrosine phosphorylation in CHO/hIR cells. 相似文献
978.
Jian Liu Yu Wen Lina Gao Liang Gao Fengjun He Jingxian Zhou 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):72-84
Abstract Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0?nM) and modest anti-proliferative activity (IC50 = 785.8?nM). Through two rounds of optimisation, the indazole derivative 9?u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3?nM) and cellular activity (IC50 = 468.2?nM). Moreover, 9?u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1. 相似文献
979.
M. Gopalakrishnan J. Thanusu V. Kanagarajan R. Govindaraju 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):52-58
New 3-chloro-1-hydroxy-2,6-diarylpiperidin-4-ones 18–22 were synthesized, characterized by melting point, elemental analysis, MS, FT-IR, one-dimensional NMR (1H & 13C) spectroscopic data and evaluated for their in vitro antibacterial and antifungal activities. All the newly synthesized compounds exerted a wide range of antibacterial activities against the entire tested gram-positive and gram-negative bacterial strains except Escherichia coli. Compounds 21 and 22 exerted strong antifungal activities against Aspergillus flavus, mucor and Microsporum gypsuem. In addition, compound 20 was more potent against Rhizopus. 相似文献
980.
Thomas Gelsing Carlsen Astrid Hjelholt Anne Grethe Jurik Berit Schi?ttz-Christensen Anna Zejden Gunna Christiansen Bent Deleuran Svend Birkelund 《Arthritis research & therapy》2013,15(3):R61