Zinc perchlorate catalyzed one-pot amination-annulation of α-cyanomethyl-β-ketoesters in water. Regioselective synthesis of 2-aminopyrrole-4-carboxylates

In this paper, we report the efficient and regioselective synthesis of 2-aminopyrrole-4-carboxylates as derivatives of conformationally restricted analogues of γ-amino butyrates (GABA) via a zinc perchlorate catalyzed amination-annulation of α-cyanomethyl-β-ketoesters under mild reaction conditions in water.     

Determination of GABA, glutamate and carbamathione in brain microdialysis samples by capillary electrophoresis with fluorescence detection

Disulfiram has been used as a deterrent in the treatment of alcohol abuse for almost 60 years. Our laboratory has shown that a disulfiram metabolite, S‐(N,N‐diethylcarbamoyl) glutathione (carbamathione), is formed from disulfiram and appears in the brain after the administration of disulfiram. Carbamathione does not inhibit aldehyde dehydrogenase but has been shown to be a partial non‐competitive inhibitor of the N‐methyl‐D ‐aspartic acid glutamate (Glu) receptor. In light of disulfiram's apparent clinical effectiveness in cocaine dependence, and carbamathione's effect on the N‐methyl‐D ‐aspartic acid receptor, the effect of carbamathione on brain Glu and γ‐aminobutyric acid (GABA) needs to be further examined. A CE‐LIF method based on derivatization with napthalene‐2,3‐dicarboxyaldehyde to simultaneously detect both neurotransmitter amino acids and carbamathione in brain microdialysis samples is described. The separation of Glu, GABA and carbamathione was carried out using a 50 mmol/L boric acid buffer (pH 9.6) on a 75 cm×50 μm id fused‐silica capillary (60 cm effective) at +27.5 kV voltage with a run time of 11 min. The detection limits for Glu, GABA and carbamathione were 6, 10 and 15 nmol/L, respectively. This method was used to monitor carbamathione and the amino acid neurotransmitters in brain microdialysis samples from the nucleus accumbens after the administration of an intravenous dose of the drug (200 mg/kg) and revealed a carbamathione‐induced change in GABA and Glu levels. This method demonstrates a simple, rapid and accurate measurement of two amino acid neurotransmitters and carbamathione for in vivo monitoring in the brain using microdialysis sampling.     

Anxiolytic potency of iridoid fraction extracted from Valeriana jatamansi Jones and its mechanism: a preliminary study

Valeriana jatamansi Jones (V. jatamansi) has been widely used for treating anxiety and its mechanism involves many aspects including GABA level. This study aimed to evaluate the anxiolytic potency of an iridoid fraction extracted from the radix and rhizomes of V. jatamansi. The iridoid fraction was extracted by using D101 resin; its major components were analysed preliminarily by thin layer chromatography, ultraviolet spectrophotometry and high-performance liquid chromatography; and its anxiolytic effects at 6 mg/kg (low-dose), 9 mg/kg (medium-dose) and 12 mg/kg (high-dose) were evaluated using the elevated plus maze test, the light–dark box test, the Vogel’s drinking conflict test, and the open field drink test. Its action mechanism was investigated using the ELISA. This study provided evidence on the anxiolytic potency of the iridoid fraction from V. jatamansi and revealed its action mechanism of regulating the GABA level.     

Comparative study of polyaromatic and polyheteroaromatic fluorescent photocleavable protecting groups

Fluorescent conjugates of N-benzyloxycarbonyl protected γ-aminobutyric acid were prepared by coupling to its C-terminus several polyheteroaromatic, based on the oxobenzopyran skeleton (trivially known as coumarin) and polyaromatic labels, such as naphthalene and pyrene. Photophysical properties were evaluated, as well as their behaviour towards photocleavage by irradiation in MeOH/HEPES buffer solution (80:20), in a photochemical reactor at different wavelengths (254, 300, 350 and 419 nm), followed by HPLC/UV monitoring.     

Fermented Oyster Extract Attenuated Dexamethasone-Induced Muscle Atrophy by Decreasing Oxidative Stress

It is well known that oxidative stress induces muscle atrophy, which decreases with the activation of Nrf2/HO-1. Fermented oyster extracts (FO), rich in γ-aminobutyric acid (GABA) and lactate, have shown antioxidative effects. We evaluated whether FO decreased oxidative stress by upregulating Nrf2/HO-1 and whether it decreased NF-κB, leading to decreased IL-6 and TNF-α. Decreased oxidative stress led to the downregulation of Cbl-b ubiquitin ligase, which increased IGF-1 and decreased FoxO3, atrogin1, and Murf1, and eventually decreased muscle atrophy in dexamethasone (Dexa)-induced muscle atrophy animal model. For four weeks, mice were orally administered with FO, GABA, lactate, or GABA+Lactate, and then Dexa was subcutaneously injected for ten days. During Dexa injection period, FO, GABA, lactate, or GABA+Lactate were also administered, and grip strength test and muscle harvesting were performed on the day of the last Dexa injection. We compared the attenuation effect of FO with GABA, lactate, and GABA+lactate treatment. Nrf2 and HO-1 expressions were increased by Dexa but decreased by FO; SOD activity and glutathione levels were decreased by Dexa but increased by FO; NADPH oxidase activity was increased by Dexa but decreased by FO; NF-κB, IL-6, and TNF-α activities were increased by Dexa were decreased by FO; Cbl-b expression was increased by Dexa but restored by FO; IGF-1 expression was decreased by Dexa but increased by FO; FoxO3, Atrogin-1, and MuRF1 expressions were increased by Dexa but decreased by FO. The gastrocnemius thickness and weight were decreased by Dexa but increased by FO. The cross-sectional area of muscle fiber and grip strength were decreased by Dexa but increased by FO. In conclusion, FO decreased Dexa-induced oxidative stress through the upregulation of Nrf2/HO-1. Decreased oxidative stress led to decreased Cbl-b, FoxO3, atrogin1, and MuRF1, which attenuated muscle atrophy.     

人脑 GABA-MRS 中回顾性运动校正方法研究

运动会影响? -氨基丁酸(GABA)磁共振谱图质量,因此,数据采集后应对是否运动加以辨别并对运动的波谱数据作相应处理．该文报道了 GABA 磁共振活体波谱测量中回顾性运动校正后处理方法．该后处理方法通过残余水峰来判断被试扫描过程中的头部运动,重建时舍弃受运动影响的数据,从而改善最终得到的编辑谱的质量．同时该文将这种运动校正方法集成到 MEGA-PRESS 序列的重建模块中,使得扫描完成后能直接得到运动校正后的编辑谱,并可采用 LCModel 对编辑谱进行定量分析．研究结果表明,这种方法可以有效去除受运动影响的数据,使得最终得到的谱图质量明显改善,从而为医学诊断和研究提供便利．
     

两种非蛋白氨基酸的新功能: 与丙二醛相互反应的机制

丙二醛(MDA)是生物分子氧化的典型羰基中间体, 是脂质过氧化的典型终末产物. 这类活性羰基中间体引起组织蛋白的老化与恶化及DNA损伤. 牛磺酸在人体内具有非常广泛的生理功能, 而g-氨基丁酸(GABA)是神经系统的一种重要抑制性神经递质, 因此二者是两种很重要的非蛋白氨基酸. 研究了在生理条件下牛磺酸或GABA是否直接诱捕MDA从而保护组织蛋白不受伤害. 将牛磺酸或GABA与MDA在生理条件下温浴48 h, 经高效液相、质谱等分析手段分析, 发现牛磺酸或GABA与MDA直接反应, 通过HPLC分离, 都生成两种主产物, 一种是没有荧光的紫外吸收峰为274～278 nm 的产物, 一种是有荧光的产物, 这种类似脂褐素(Ex. 392～395 nm/Em. 456～364 nm)的荧光产物是1,4-二氢吡啶衍生物. 牛磺酸或GABA与MDA的反应表明它们在生理条件下具有清除活性羰基的功能, 而这种毒性羰基与很多羰基紧张相关的疾病及衰老有关.     

A New Synthesis Method and GABA Transporters Inhibitory Activities of Tiagabine and Its Analogues

IntroductionγAminobutyricacid(GABA)isrecognizedasthe principalbraininhibitoryneurotransmitter.GABAup takefromthesynapticcleftisoneoftheimportant mechanismsintheregulationofGABAactivity.Inhibi tionoftheuptakeofGABAbypotentandselectivein hibitorsoftheGABAt…     

Design, Synthesis, and Hypnotic Activity of Pyrazolo [1,5-a]pyrimidine Derivatives

On the basis of the Zaleplon structure, novel pyrazolo[1,5-a]pyrimidines were designed and prepared for studies on their hypnotic activity. This paper reported the synthesis of twelve new 5-methyl-7-substituted-pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives by using simple starting materials such as propane dinitrile and triethyl orthoformate. The structures of the derived target compounds were confirmed by their IR and ^1H-NMR spectroscopic data. The preliminary pharmacological evaluations indicated that some compounds showed hypnotic activity, whilc derivative 1c was the most potent one.     

First asymmetric syntheses of 6-substituted nipecotic acid derivatives

Various nipecotic acid derivatives are known to be potent GABA uptake inhibitors thus being useful in the treatment of a number of neurological and psychological disorders. In this paper, the first asymmetric syntheses of 6-substituted nipecotic acid derivatives are presented. The synthetic strategy was designed to provide access to a large variety of enantiomerically pure 6-substituted nipecotic acid derivatives. The synthesis starts from the chiral N-acyldihydropyridines 15 and 16 obtained via asymmetric electrophilic α-amidoalkylation reaction of a chiral N-acylpyridinium ion. These were utilized for the preparation of enantiomerically pure 6-(4,4-diphenylbutyl)nipecotic acids and 6-(4,4-diphenylbutenyl)nipecotic acids in a multistep synthesis, including the removal of the dimethylphenylsilyl blocking group from the dihydropyridine ring, the reduction of the dihydropyridine heterocycle, a Horner-Wittig reaction and the removal of the chiral auxiliary. The obtained target molecules, however, showed only negligible affinity to the GAT-1- and GAT-3 transport proteins.