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71.
The importance of Ca2+ signaling in astrocytes is undisputed but a potential role of Ca2+ influx via L-channels in the brain in vivo is disputed, although expression of these channels in cultured astrocytes is recognized. This study shows that an increase in free cytosolic Ca2+ concentration ([Ca2+]i) in astrocytes in primary cultures in response to an increased extracellular K+ concentration (45 mM) is inhibited not only by nifedipine (confirming previous observations) but also to a very large extent by ryanodine, inhibiting ryanodine receptor-mediated release of Ca2+, known to occur in response to an elevation in [Ca2+]i. This means that the actual influx of Ca2+ is modest, which may contribute to the difficulty in demonstrating L-channel-mediated Ca2+ currents in astrocytes in intact brain tissue. Chronic treatment with any of the 3 conventional anti-bipolar drugs lithium, carbamazepine or valproic acid similarly causes a pronounced inhibition of K+-mediated increase in [Ca2+]i. This is shown to be due to an inhibition of capacitative Ca2+ influx, reflected by decreased mRNA and protein expression of the ‘transient receptor potential channel’ (TRPC1), a constituent of store-operated channels (SOCEs). Literature data are cited (i) showing that depolarization-mediated Ca2+ influx in response to an elevated extracellular K+ concentration is important for generation of Ca2+ oscillations and for the stimulatory effect of elevated K+ concentrations in intact, non-cultured brain tissue, and (ii) that Ca2+ channel activity is dependent upon availability of metabolic substrates, including glycogen. Finally, expression of mRNA for Cav1.3 is demonstrated in freshly separated astrocytes from normal brain. 相似文献
72.
Federica Prati Manuela Bartolini Elena Simoni Angela De Simone Antonella Pinto Vincenza Andrisano Maria Laura Bolognesi 《Bioorganic & medicinal chemistry letters》2013,23(23):6254-6258
The anti-amyloid properties shared by several quinones inspired the design of a new series of hybrids derived from the multi-target drug candidate memoquin (1). The hybrids consist of a central benzoquinone core and a fragment taken from non-steroidal anti-inflammatory drugs, connected through polyamine linkers. The new hybrids retain the potent anti-aggregating activity of the parent 1, while exhibiting micromolar AChE inhibitory activities. Remarkably, 2, 4, (R)-6 and (S)-6 were Aβ aggregation inhibitors even more potent than 1. The balanced amyloid/cholinesterase inhibitory profile is an added value that makes the present series of compounds promising leads against Alzheimer’s disease. 相似文献
73.
Hua Chen Shuai Li Yuchao Yao Likai Zhou Jianpeng Zhao Yunjing Gu Kerang Wang Xiaoliu Li 《Bioorganic & medicinal chemistry letters》2013,23(17):4785-4789
Novel triphenylethylene–coumarin hybrid derivatives containing different amounts of amino side chains were designed and synthesized in good yields under microwave radiation. The derivatives 5b–d which possessed two amino side chains (except morpholinyl) showed a broad-spectrum and good anti-proliferative activity against five tumor cells and low cytotoxicity in osteoblast. UV–vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation exhibited that compounds 10c, 5c, and 13c bearing amino side chain (except morpholinyl) on 4-phenyl had significant interactions with Ct-DNA by the intercalative mode of binding. Structure–activity relationships (SARs) analysis suggested that the amino alkyl chain would play an important role both in the compounds against tumor cells proliferation and their interactions with DNA. 相似文献
74.
75.
This review focuses on the syntheses of PI3K/Akt/mTOR inhibitors that have been reported outside of the patent literature in the last 5 years but is largely centered on synthetic work reported in 2011 and 2012. While focused on syntheses of inhibitors, some information on in vitro and in vivo testing of compounds is also included. Many of these reported compounds are reversible, competitive adenosine triphosphate (ATP) binding inhibitors, so given the structural similarities of many of these compounds to the adenine core, this review presents recent work on inhibitors based on where the synthetic chemistry was started, that is, inhibitor syntheses which started with purines/pyrimidines are followed by inhibitor syntheses which began with pyridines, pyrazines, azoles, and triazines then moves to inhibitors which bear no structural resemblance to adenine: liphagal, wortmannin and quercetin analogs. The review then finishes with a short section on recent syntheses of phosphotidyl inositol (PI) analogs since competitive PI binding inhibitors represent an alternative to the competitive ATP binding inhibitors which have received the most attention. 相似文献
76.
77.
《Bioscience, biotechnology, and biochemistry》2013,77(9):1948-1955
Allicin (allyl 2-propenethiosulfinate), an antibacterial principle of garlic, has drawn much attention, since it has potent antimicrobial activity against a range of microorganisms, including methicillin-resistant Staphylococcus aureus. There have been many reports on the antibacterial properties of allicin, but no quantitative comparison of antibacterial activities between freshly prepared garlic extract and clinically useful antibiotics has been performed. To verify the substantial antibacterial effect of aqueous garlic extract, we compared it with those of allicin and several clinically useful antibiotics using two representative bacteria commonly found in the human environment, Gram-positive S. aureus and Gram-negative Escherichia coli. The garlic extract had more potent anti-staphylococcal activity than an equal amount of allicin. In terms of antibiotic potency against Gram-positive and Gram-negative bacteria, authentic allicin had roughly 1–2% of the potency of streptomycin (vs. S. aureus), 8% of that of vancomycin (vs. S. aureus), and only 0.2% of that of colistin (vs. E. coli). The antibacterial activity of allicin was completely abolished by cysteine, glutathione and coenzyme A, but not by non-SH-compounds. The oxygen in the structure (–S(=O)–S–) of allicin therefore functions to liberate the S-allyl moiety, which might be an offensive tool against bacteria. 相似文献
78.
目的:探究甲基强的松龙联合中剂量环磷酰胺(CTX)治疗重症肌无力危象(MGC)的临床效果及安全性。方法:选取2012年1月~2015年6月在我院神经内科就诊的MGC患者90例,随机分为对照组(45例)和观察组(45例),对照组患者接受甲基强的松龙治疗,观察组采用甲基强的松龙联合中剂量CTX治疗。比较两组患者的临床疗效及不良反应的发生情况。结果:观察组患者呼吸困难消失时间、吞咽功能恢复时间和肢体无力症状改善时间均明显短于对照组(P0.05);观察组用药7 d内治疗有效率86.7%明显高于对照组(P0.05),肺部感染发生率20%,较对照组显著降低,差异均具有统计学意义(P0.05)。结论:甲基强的松龙联合中剂量CTX可有效提高MGC的治疗效果,促进患者早日康复,且肺部感染的发生率降低。 相似文献
79.
Two new cembranoids, together with fifteen known ones, were isolated from the flowers of Nicotiana tabacum L. The structures of the new compounds were established as (1βH,2E,4αOH,6αOH,7E,10αH,11αH,12βOH)-10,11-epoxy-2,7-cembradiene-4,6,12-triol (1) and (1βH,2E,4αOH,6αOH,7E,10βH,11βH,12αOH)-10,11-epoxy-2,7-cembradiene-4,6, 12-triol (2) by using spectroscopic analysis, including HRESIMS, IR, one- and two-dimensional NMR. A plausible biogenetic relationship of the isolated cembranoids was proposed. The antitumor activities of selected compounds against a panel of three human cancer HepG2, A549 and HCT-116 cell lines were evaluated by the MTT assay. Compound 5 exhibited moderate activity against Hep-G2 cell lines with an IC50 value of 14.38 μM. 相似文献
80.
Chemical characterization as well as antioxidant and anti-tumor activity are reported for isolated metabolites from Teucrium polium L. (Lamiaceae). Structures were identified using standard MS and NMR spectroscopic methods. Sesquiterpene absolute stereochemistry was determined based on a modified Mosher’s reaction. Biological activity was evaluated by a cupric reducing antioxidant capacity (CUPRAC) assay and select compounds screened for anti-tumor activity. (1R,4S,10R) 10,11-dimethyl-dicyclohex-5(6)-en-1,4-diol-7-one and (R)-mandelonitrile-β-laminaribioside, together with ten previously reported compounds were identified. Antioxidant versus tumor-inhibition relationships was examined. 相似文献