槲皮素及其衍生物防治肝损伤作用及机制的研究进展

槲皮素是一种多羟基黄酮类化合物,广泛存在于多种药用植物中,具有抗氧化、抗病毒、抗菌、抗炎和抗肿瘤等多种药理作用。分析了近10年国内外有关槲皮素及衍生物防治肝损伤方面的文献,发现其对各种急、慢性肝损伤均具有良好的防治作用,其作用机制主要涉及抗氧化、抗炎、调节脂质代谢、抗凋亡及自噬、抗病毒等。主要对槲皮素及其衍生物防治不同类型肝损伤的作用及机制进行综述,以期为槲皮素保肝作用的深入研究提供较为全面的文献信息支持。     

A dual‐tracer study of extrastriatal 6‐[18F]fluoro‐m‐tyrosine and 6‐[18F]‐fluoro‐l‐dopa Uptake in Parkinson's disease

6‐[¹⁸F]‐Fluoro‐l ‐dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism—its intense uptake in the striatum, and fainter uptake in other brain regions, is correlated with the symptoms and pathophysiology of Parkinson's disease (PD). 6‐[¹⁸F]fluoro‐m‐tyrosine (FMT), which also targets l ‐amino acid decarboxylase, has potential advantages over FDOPA as a radiotracer because it does not form catechol‐O‐methyltransferase (COMT) metabolites. The purpose of the present study was to compare the regional distribution of these radiotracers in the brains of PD patients. Fifteen Parkinson's patients were studied with FMT and FDOPA positron emission tomography (PET) as well as high‐resolution structural magnetic resonance imaging (MRI). MRI's were automatically parcellated into neuroanatomical regions of interest (ROIs) in Freesurfer ( http://surfer.nmr.mgh.harvard.edu ); region‐specific uptake rate constants (K_occ) were generated from coregistered PET using a Patlak graphical approach. The essential findings were as follows: (1) regional K_occ were highly correlated between the radiotracers and in agreement with a previous FDOPA studies that used different ROI selection techniques; (2) FMT K_occ were higher in extrastriatal regions of relatively large uptake such as amygdala, pallidum, brainstem, hippocampus, entorhinal cortex, and thalamus, whereas cortical K_occ were similar between radiotracers; (3) while subcortical uptake of both radiotracers was related to disease duration and severity, cortical uptake was not. These results suggest that FMT may have advantages for examining pathologic changes within allocortical loop structures, which may contribute to cognitive and emotional symptoms of PD. Synapse 68:325–331, 2014 . © 2014 Wiley Periodicals, Inc.     

Antimicrobial Activity of Novel C2-Substituted 1,4-Dihydropyridine Analogues

The antimicrobial activity of 3-methyl-5-isopropyl (or ethyl) 6-methyl-4-nitrophenyl-1,4-dihydropyridine-3,5-dicarboxylate derivatives was evaluated. Prokaryotes (bacteria) appeared to be more sensitive to their antimicrobial activity than were eukaryotes (filamentous fungi). The best antibacterial activity was shown by derivative 33, which was able to inhibit the growth of Mycobacterium smegmatis (MIC₃₃ = 9 μg.ml⁻¹), Staphylococcus aureus (MIC₃₃ = 25 μg.ml⁻¹), and Escherichia coli (MIC₃₃ = 100 μg.ml⁻¹). In addition, derivative 4 demonstrated its antibacterial power on the acid-fast bacterial species M. smegmatis and on Gram-positive S. aureus. Focusing on the structure-activity relationship, it appears that the increase in the substituent bulk at the C2 position improved the antibacterial activity of the set of compounds studied. Derivatives 33 and 4, carrying 2-cyano-3-oxo-3-phenylprop-1-en-1-yl and allyliminomethyl groups, respectively, showed significantly higher inhibition activities on all tested microorganisms in comparison with the rest of the derivatives. This enhancement was also in good correlation with different log P values (lipophilicity parameter).     

Assessment of the genotoxic and carcinogenic potentials of 3‐aminothiophene derivatives using in vitro and in silico methodologies

Thiophene derivatives, a class of compounds widely used in products such as pharmaceuticals, agrochemicals or dyestuffs, represent chemicals of concern. Indeed, the thiophene ring is often considered as a structural moiety that may be involved in toxic effects in humans. We primarily focus on the genotoxic/mutagenic and carcinogenic potentials of the methyl 3‐amino‐4‐methylthiophene‐2‐carboxylate (1), a precursor of the articaine local anesthetic (4) which falls within the scope of the European REACH (Registration, Evaluation, Authorisation and restriction of CHemicals) legislation. To discern some structure–toxicity relationships, we also studied two related compounds, namely the 3‐amino 4‐methylthiophene (2) and the 2‐acetyl 4‐chlorothiophene (3). Techniques employed to assess mutagenic and DNA‐damaging effects involved the Salmonella mutagenicity assay (or Ames test) and the single‐cell gel electrophoresis assay (or Comet assay). In the range of tested doses, none of these derivatives led to a positive response in the Ames tests and DNA damage was only observed in the Comet assay after high concentration exposure of 2. The study of their carcinogenic potential using the in vitro SHE (Syrian Hamster Embryo) cell transformation assay (CTA) highlighted the activity of compound 2. A combination of experimental data with in silico predictions of the reactivity of thiophene derivatives towards cytochrome P450 (CYP450), enabled us to hypothesize possible pathways leading to these toxicological profiles. Copyright © 2013 John Wiley & Sons, Ltd.     

2-(4-三氟甲基苯基)-4-乙基-呋喃-3-酰胺衍生物的设计、合成及其抗肿瘤活性研究

目的 设计、合成新型抗肿瘤的2-（4-三氟甲基苯基）-4-乙基-呋喃-3-酰胺衍生物.方法 以对三氟甲基苯甲醛和丙二酸二乙酯为起始原料,经缩合、环合、酰氯化及胺解等4步反应,合成系列目标化合物.结果 设计合成了15个目标化合物,并对其进行了4种肿瘤细胞A549、QGY、HeLa和SW480的活性测试.结论 显示出较好的抗肿瘤活性,化合物5b显示出最优的高效、广谱抗肿瘤活性,值得深入研究.     

Design,Synthesis, and Preliminary Activity Evaluation of Novel Pyrimidine Derivatives as Acid Pump Antagonists

Acid-related diseases of the upper gastrointestinal tract, especially gastroesophageal reflux disease (GERD), remain a widespread problem worldwide. In this paper, we reported the design, synthesis, and preliminary gastric antisecretory activity evaluation of novel pyrimidine derivatives as acid pump antagonists. The gastric antisecretory activity assay results showed that all compounds displayed potent gastric antisecretory activity when gastric secretion was stimulated by histamine. The most potent compound 5g exhibited even similar gastric antisecretory activity compared with the control revaprazan, and the relative inhibition rate was 93.0%, which was worthy of further investigation.     

Syntheses,Cholinesterases Inhibition,and Molecular Docking Studies of Pyrido[2,3‐b]pyrazine Derivatives

Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3‐b]pyrazines ( 6a ‐ 6q ) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3‐b]pyrazines showed 3‐(3′‐nitrophenyl)pyrido[2,3‐b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC₅₀ values of 0.466 ± 0.121 and 1.89 ± 0.05 μm , respectively. The analogues 3‐(3′‐methylphenyl)pyrido[2,3‐b]pyrazine 6c and 3‐(3′‐fluorophenyl)pyrido[2,3‐b]pyrazine 6f were found to be selective inhibition for BChE with IC₅₀ values of 0.583 ± 0.052 μm and AChE with IC₅₀ value of 0.899 ± 0.10 μm , respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors.