The Antioxidization Effects of TP-5, Thy(1[Lys23] and Their Spin Labeled Derivatives

TP-5 and Thy(1, synthesized by solid phase synthesis, have the effect to restrain the formation of superoxide anion in xanthine oxidase system in vitro. The formations of lipid peroxide in several organs (such as liver, brain and thymus) of the mice treated with TP-5, TP-5(R, active fragment of Thy(1 and active fragment of Thy(1(R of 10 (g(kg(d-1 for 10 d were decreased. That means these peptides possess the capability of antioxidezation.

Synthesis and antitumor activity of N^1-acetylamino-(5-alkyl/aryl-1,3,4-thiadiazole-2-yl)-5-fluorouracil derivatives

A new series of N^1-acetylamino-（5-alkyl/aryl- 1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives were designed and synthesized. These compounds have not been reported in literature, and their structure chemical were confirmed by IR, ^1H NMR and MS （HRMS）. The results of antitumor inhibitory activity test showed that some compounds possess more potent antitumor inhibitory activity than 5-fluorouracil.

Synthesis and antiangiogenic activities of 5-amino-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanoic acid derivatives

Based on the structure-activity relationships and antiangiogenic mechanism of RGD-containing peptides, a series of 5-amino- 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. The structures were characterized by ^1H NMR, MS and elementary analysis. There ability to inhibit angiogenesis were evaluated by chick embryo chorioallantoic membrane assay at 10^-5 mol/L. Compounds 7a and 7b displayed obvious antiangiogenic activity.

2D-QSAR Studies on Anthranilic Acid Derivatives: A Novel Class of Allosteric Inhibitors of Hepatitis C NS5B Polymerase

Quantitative structure activity relationship （QSAR） studies were performed on 45 anthranilic acid derivatives for their potent allosteric inhibition activities of HCV NSSB polymerase. Genetic algorithm based genetic function approximation （GFA） method of variable selection was used to generate the model. Highly statistically significant model with r^2 = 0.966 and r^2cv = 0.951 was obtained when the number of descriptors in the equation was set to 5. High r^2pred value of 0.884 indicates the good predictive power of the best model. Spatial descriptors of radius of gyration （RadOfGration）, molecular volume （Vm）, length of molecule in the z dimension （Shadow-Zlength）, thermodynamic descriptors of the octanol/water partition coefficient （LogP） and molecular refractivity index （MR） showed enormous contributions to HCV NS5B polymerase inhibition. The validation of the model was done by leave-one-out （LOO） test, randomization tests and external test set prediction. The model gives insight on indispensable structural requirements for the activity and can be used to design more potent analogs against HCV NSSB polymerase.

Design,Synthesis,and Biological Evaluation of 5H-Thiazolo[3,2-a]pyrimidine-6-carboxylic Acid Ethyl Ester Derivatives as a Novel Series of Acetylcholinesterase Inhibitors

Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibitors was designed based on virtual screening methods. The target compounds were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, ^1H NMR, and ^13C NMR. The biological evaluation against human acetylcholinesterase in vitro indicated all the target compounds show more than 50% inhibition at 10μmol/L by means of the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer＇s disease and lay the foundation of searching for improved acetylcholinesterase inhibitors with the novel scaffolds.

Photodynamic Therapy of Cancer Cells with Methanesulfonate Salts of 5-Aminolevulinic Acid and Its Derivatives

A series of 5-aminolevulinic acid and its alkylester methanesulfonates was exploited to photodynamic therapy（PDT） of human lymphocytic cells, U-937 in vitro. The PDT efficiency is influenced by the concentration and incubation time. Generally, for ALA and its alkylester methanesulfonates, the cell survival rate decreases and the accumulation ability of PplX increases with the concentration and incubation time. We found that the longer carbon chain methanesulfonates（C5-S, C6-S, C8-S） exhibit better PDT effect than ALA methanesulfonate. This possibly provides a promising route to the clinical application ofPplX-mediated PDT to cancer cell.

Synthesis and Anti-influenza Virus Activity of Ethyl 6-Bromo-5-hydroxyindole-3-carboxylate Derivatives

A series of ethyl 6-bromo-5-hydroxyindole-3-carboxylate derivatives were synthesized and their in vitro anti-influenza virus activity was evaluated. All the compounds were characterized by 1H NMR and MS.

Design, Synthesis and Antifungal Activity of 6-Fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]-quinoline-2-carboxamide Derivatives

A series of 6-fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]quinoline-2-carboxamide derivatives was designed based on the bioisosterism and combination principle in drug design. The target compounds were synthesized from substituted aniline through Michael addition, cyclization, Mannich reaction and condensation with 4-substituted semicarbazides, and the structures were confirmed by mass spectrometry（MS） and 1H NMR. The antifungal assay was carried out in vitro by two-fold dilution. The result shows that all the compounds are of antifungal activities against the tested fungi at different levels.

Synthesis, Crystal Structure and Antitumor Activities of N,N,1-Triphenyl-1H-benzo[d]imidazol-5-amine Derivatives

In order to discover the novel antitumor agents,a series of N,N,1-triphenyl-1Hbenzo[d]imidazol-5-amine derivatives were designed and synthesized,and the structures were characterized by IR,H-RMS,1H and 13C NMR.X-ray crystallography showed that 4c is in monoclinic system,space group P1 with a=9.209(2),b=9.533(3),c=14.097(3)?,β=102.069(3)°,V=1202.2(5)?3,Z=2,F(000)=528,μ=1.74 mm–1,S=1.024,the final R=0.0448 and wR=0.1109.The in vitro antitumor activities of target compounds were evaluated by MTT assay against human cancer cell lines K562,HL-60,HeLa and BGC-823.The target compounds demonstrated weak or moderate antitumor activities against these cell lines.

SYNTHESIS OF ADENOSINE DERIVATIVES WITH CARBOXYALKYL SIDE CHAIN AT 2',3'OR 5'POSITION

Some nucleoside carhoxylic acid derivatives,such as(±)ethyl ester of griseolic acid (4)and 9-(2'-deoxy-2'-(benzyloxycarbonyl)-methylene-β-D-rihohept-2'-enofuranosyluranate)adenine (11),were synthesized.The formation of lactone of 5'-deoxy-adenosineacetic acid(AAA,3)was investigated by using different reagents for lactonization from AAA,but all of the efforts failed, and sone unexpected compounds were obtained.

A FACILE SYNTHESIS OF HETEROCYCLE SUBSTITUTED CHALCONE AND 5-NITROFURANYL OLEFIN DERIVATIVES

Reaction of heterocycle substituted telluronium salts with aroma- tic aldehydes under mild conditions gave corresponding chalcones.In the presence of dibutyl telluride,2-bromomethyl-5-nitrofuran condensed easily with aromatic aldehydes in THF to afford corresponding olefin derivatives as one-pot reaction.

SYNTHESIS OF HETEROCYCLICCARBOXYLIC DERIVATIVES OF TITANOCENE MOLECULAR STRUCTURE OF (CH_3C_5H_4)Ti((?)co_2)_2

Eight comptexes (RC_5H_4)_2Ti(O_2CA_r)_2(R=H,CH_3;Ar= with 2 equiv.N_aO_2CA_r.The carboxytate ligands in the complexes coordinate to titan^um atom in monodentate mode.(CH_3C_5H_4)_2Ti(O_2CC_4H_3S-2)_2 has four-coordinate bent titanocene in which the thiophencarboxyaltes are a monodeotate ligand(Ti-0=1.981(8)A,1.926(3)A;) 0-Ti-0:91.6(8)~ ; Ti-C:2.333-2.440A).

STUDIES ON THE SYNTHESIS OF D-GLUCURONIC ACID DERIVATIVES OF 2-BUTOXY-5-FLUORO-3H-4-PYRIMIDONE AND THEIR ANTICANCER ACTIVITIES

2-Butoxy-5-fluoro-3H-4-pyrimidone derivatives of D-glucuronic acid having 0-glycosidic linkage or N-glycosidic linkage were synthesized and their anticancer activity tested.Their structures were confirmed by elementary analysis,IR spectra and ~1HNMR.

5-取代-4-氨基-3-巯基-1,2,4-三唑衍生物的应用进展

5-取代-4-氨基-3-巯基-1,2,4-三唑是一类重要的五元杂环化合物,由于分子中含有巯基和伯胺基两个活性基团,既可以单个基团参与反应生成N-或S-取代产物,又可以同时发生反应生成稠杂环化合物。由其衍生而来的化合物具有广泛的生物活性,在抗菌、抗肿瘤、抗结核、抗炎镇痛、酶抑制剂、荧光探针等方面都表现出优异的性能。综述了近年来5-取代-4-氨基-3-巯基-1,2,4-三唑衍生物在医学、农业及材料领域的应用,为今后进一步研究、开发此类化合物提供参考。

头穴针刺联合密集训练治疗孤独症谱系障碍患儿疗效观察及对血清5-HT、BDNF的影响

目的:观察头穴针刺联合密集训练对孤独症谱系障碍(ASD)患儿核心症状及血清5-羟色胺(5-HT)、脑源性神经营养因子(BDNF)的影响。方法:将ASD患儿102例按随机数字表法分为对照组和治疗组各51例。对照组采取常规密集训练治疗,治疗组在对照组基础上联合头穴针刺治疗。比较2组治疗前后孤独症行为(ABC)、儿童孤独症评定量表(CARS)、孤独症治疗评估量表(ATEC)和父母育儿压力指数简表(PSI-SF)评分,以及血清5-HT、BDNF水平。结果:治疗后,2组ABC、CARS、ATEC评分均治疗前降低(P<0.05),且治疗组ABC、CARS、ATEC评分均低于对照组(P<0.05)。治疗后,2组感觉能力、交往能力、躯体运动能力、语言能力和自我照顾能力等ABC量表中各因子评分均较治疗前降低(P<0.05),且治疗组上述各项评分均低于对照组(P<0.05)。治疗后,2组PSI-SF总分及育儿愁苦、亲子互动失调、困难儿童3个维度评分均较治疗前降低(P<0.05),且治疗组上述各项评分均低于对照组(P<0.05)。治疗后,2组血清5-HT水平较治疗前降低(P<0.05),BDNF水平较治疗前升高(P<0.05);且治疗组5-HT水平低于对照组(P<0.05),BDNF水平高于对照组(P<0.05)。结论:头穴针刺联合密集训练能有效调节血清5-HT、BDNF水平,改善ASD患儿的核心症状,减轻父母育儿压力,提高整体治疗效果。

温胆汤对抑郁症患者血清脑源性神经生长因子、5-羟色胺水平的影响

目的探讨温胆汤对抑郁症患者血清脑源性神经生长因子(BDNF)、5-羟色胺(5-HT)水平的影响。方法选取2022年1月至2023年4月江苏省苏州市广济医院抑郁症患者100例,按照随机数字表法将其分为观察组和对照组,各50例。对照组给予常规抗抑郁药物,观察组在对照组基础上联合温胆汤。两组均持续治疗8周。比较两组临床疗效,同时比较治疗前后中医证候积分,另外测定两组治疗前后血清BDNF、5-HT水平,最后比较两组不良反应发生情况。结果观察组临床疗效优于对照组,差异有统计学意义(P<0.05)。治疗前,两组中医症候积分比较,差异无统计学意义(P>0.05);治疗后,两组中医症候积分治疗前降低,且观察组低于对照组,差异有统计学意义(P<0.05)。治疗前,两组血清BDNF、5-HT水平比较,差异无统计学意义(P>0.05);治疗后,两组血清BDNF、5-HT水平较治疗前升高,且观察组高于对照组,差异有统计学意义(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论温胆汤用于治疗抑郁症不仅能有效改善患者临床症状,还能改善其血清BDNF、5-HT水平,且具备安全性。

血5′tRF-LysCTT对急性脑梗死早期诊断及病情严重程度判定的价值

目的探究血5′tRF-LysCTT表达水平对急性脑梗死(ACI)患者早期诊断及病情严重程度判定的价值。方法收集2022年10月至2023年10月在哈尔滨医科大学附属第一医院神经内科住院急性脑梗死(ACI)患者为ACI组(n=114),选取同期健康体检者为对照组(n=112)。根据NIHSS评分将ACI患者分为轻型组(NIHSS≤5分,n=66)和中重型组(NIHSS>5分,n=48)。通过实时荧光定量聚合酶链反应(RT-qPCR)技术检测两组血5′tRF-LysCTT水平。应用多因素Logistic回归分析预测ACI患者神经功能缺损程度的危险因素。ROC曲线分析5′tRF-LysCTT对区分轻型、中重型ACI的诊断价值。结果ACI患者血5′tRF-LysCTT水平明显低于对照组(1.34±0.56 vs.3.28±1.01,P<0.001)。与轻型组比较,中重型组血5′tRF-LysCTT表达明显降低(1.65±0.45 vs.0.89±0.36,P<0.001)。与5′tRF-LysCTT相对表达量与ACI神经功能缺损程度呈负相关(P<0.001)。ROC曲线分析5′tRF-LysCTT对区分ACI组与对照组的曲线下面积(AUC值)为0.956(95%CI 0.9317~0.9805),敏感度为94.6%,特异度为84.7%,截断值为2.11;区分ACI轻、中重型的AUC值为0.908(95%CI 0.8543~0.9618),敏感度为93.3%,特异度为80.2%,截断值为1.41,具有较高诊断效率。Logistic回归分析显示,5′tRF-LysCTT是预测神经功能缺损程度的独立危险因素。结论血5′tRF-LysCTT可能成为ACI患者早期诊断及病情严重程度判定的新标志物。

An enriched environment increases the expression of fibronectin type Ⅲ domain-containing protein 5 and brain-derived neurotrophic factor in the cerebral cortex of the ischemic mouse brain

Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.

脑源性神经营养因子和神经营养因子-5在女性生殖内分泌领域的研究进展

脑源性神经营养因子(BDNF)和神经营养因子-5(NT-5)属于神经营养因子家族,是一类由神经支配的靶组织分泌的分泌型多肽,两者通过作用于相同的受体发挥作用。BDNF和NT-5在卵巢表达广泛,发挥着促进卵泡组装和发育、卵母细胞成熟、排卵、调节颗粒细胞和膜细胞类固醇激素分泌等多种生理作用。不孕症是由多种病因导致的一种生育障碍状态,不孕症患者卵巢局部的BDNF和NT-5存在异常分泌情况。因此,了解BDNF和NT-5在女性生殖内分泌领域的研究进展,可能为不孕症治疗提供新方向,为辅助生殖结局的预测提供新指标。