1-烯丙基-6-氯-7-甲基-1,4-二氢喹喔啉-2,3-二酮的合成

设计并合成了化合物1 烯丙基 6 氯 7 甲基 1,4 二氢喹喔啉 2,3 二酮,该化合物主要用于一系列新型NMDA受体拮抗剂的制备。反应以1 氯 4 氟 2 甲基苯为原料,在浓硫酸溶液中采用硝酸钾硝化得1 氯 4 氟 2 甲基 5 硝基苯,收率94 0%,将1 氯 4 氟 2 甲基 5 硝基苯与烯丙胺反应,三乙胺为缚酸剂,回流反应合成烯丙基 (4 氯 5 甲基 2 硝基 苯基) 胺,收率为81 0%,然后使用铁粉高收率还原所得的硝基化合物(收率为95 0%),再与二水合草酸在c(HCl)=2mol/L的盐酸中进行环合反应合成目的化合物1 烯丙基 6 氯 7 甲基 1,4 二氢喹喔啉 2,3 二酮(收率为90 6%),反应总收率为65 5%。     

1,4-二氧喹喔啉甲醛双腙的合成及除草活性研究

用1,4-二氧-2-喹喔啉甲醛、水杨醛、甲醛、乙醛、丙酮、丁烯醛、环戊酮和环己酮与水合肼反应制备了8种中间体单腙,再用这些单腙与1,4-二氧-2-喹喔啉甲醛反应合成了8种双腙新化合物,并进行了表征。对这些新化合物对油菜和稗草进行了除草活性研究。研究结果表明1,4-二氧喹喔啉-2-甲醛-水杨醛双腙和1,4-二氧喹喔啉-2-甲醛-丙酮双腙表现较明显的活性,在500mg/L浓度时对稗草的株防效分别为51 3%和55 0%;对油菜株防效较弱,分别只有33 5%和17 5%。     

喹喔啉类化合物的合成研究进展

喹喔啉是一种重要的精细化工中间体,广泛用于农药,医药等行业,本文以二羰基,二硫代碳基,环氧化合物,α-羟基酮,α,β-二醇以及α-卤代酮与邻苯二胺为原料,综述了近些年来过渡金属与无过渡金属条件下喹喔啉合成方法的研究进展。报道了化学家们在合成喹喔啉这一领域里的合成方法,并对喹喔啉合成的研究前景进行了展望。     

一种新型吲哚并咔唑化合物的合成与表征

5-([1,1′-二联苯]-4-基)-5,11-二氢吲哚[3,2-b]咔唑为有机电致发光材料和光电催化材料重要中间体。以3-溴咔唑和4-碘联苯为原料,经过Ullmann反应、Buchwald-Hartwig偶联反应和分子内Heck偶联反应生成目标化合物。通过对催化剂、配体和溶剂等条件的优化,确定合成9-[1,1′-联苯-4-基]-3-溴-9H-咔唑的最佳工艺为:催化剂为氯化亚铜、配体为1,10-菲罗啉、溶剂为N,N-二甲基甲酰胺(DMF);目标化合物提纯的最优条件为6倍体积四氢呋喃。合成的化合物经高效液相色谱仪(HPLC)测试纯度,差示扫描量热仪(DSC)测试熔点,核磁共振(~1HNMR、~(13)CNMR)确定结构。     

喹喔啉化合物的脂质过氧化活性

研究了一系列先前合成的喹喔啉化合物的抑制脂质过氧化活性,实验得到了这些化合物的体内和体外脂质过氧化抗氧化活性数据,发现这类喹喔啉化合物具有优异的抗氧化活性,其中,脂质过氧化清除率最高的化合物是2-(3-(3-甲氧基-4-羟基苯基)-2氧喹喔啉-1(2H)-烷基)乙酸,它在浓度为100μmol/L时,对应的清除率达到了57.7%。构效关系研究认为对羟基苯乙烯这一结构单元对于喹喔啉化合物在提高抗氧化活性有重要意义。     

3-氯-2,6-二硝基喹喔啉的合成工艺研究

喹喔啉为一类重要的苯并吡嗪类杂环化合物,喹喔啉衍生物在医药及化工合成领域具有重要的作用。3-氯-2,6-二硝基喹喔啉是一种重要医药化工中间体。本文以2-羟基喹喔啉为原料,经硝化反应和氯代反应两步反应得到目标化合物。该合成方法操作简便、后处理操作简便,花费时间少且产物纯度高、收率也较高,产品收率为58.2%,适合工业化生产。     

1,4-二氧喹喔啉-2-甲醛酰腙的合成和除草活性研究

用取代脂肪酸酯、取代苯甲酸酯和二酸酐与水合肼反应制备了13种中间体酰肼。所得酰肼与1,4 二氧喹喔啉 2 甲醛反应合成了13种新化合物1,4 二氧喹喔啉 2 甲醛酰腙。用元素分析、MS、IR和1HNMR对这些酰腙的结构进行了表征,并且用这些化合物对稗草和油菜进行了除草活性研究。研究结果显示,化合物在质量浓度为250mg/L时株防效大都在20%以下,质量浓度为500mg/L时株防效才会达到20%～30%。1,4 二氧喹喔啉 2 甲醛 γ 羟基丁酰腙在质量浓度为500mg/L时对白菜和稗草的株防效分别达到74%和56%。     

厄达替尼的新合成方法

设计并完成厄达替尼(1)新的汇聚式合成工艺路线，优化得到50 g级别的目标产物。采用市场易于购买的原料喹喔啉-2-醇、4-溴-1-甲基-1H-吡唑、2-溴-1,1-二甲氧基乙烷等为起始原料，制备得到关键中间体3,5-二甲氧基苯基异丙基乙烷-1,2-二胺(17),2步反应收率89%,纯度98.8%。化合物17和7-溴-2-(1-甲基-1H-吡唑-4-基)喹喔啉(8)偶联得到厄达替尼，收率为89%,纯度为99.4%,7步反应总收率54%。     

4-（6-氯喹喔啉-2-氧基）苯酚的合成

4-（6-氯喹喔啉-2-氧基）苯酚是合成喹禾灵和喔草酯类除草剂的重要中间体。通常采用两种方法合成这种中间体。方法一由化合物2,6-二氯喹喔啉和对苯二酚在乙腈中，在碳酸钾无机碱存在下进行缩合反应，制备4-（6-氯喹喔啉-2-氧基）苯酚；方法二由化合物2,6-二氯喹喔啉和对苯二酚在二甲基亚砜中，在氢氧化钙无机碱存在下进行缩合反应，制备4-（6-氯喹喔啉-2-氧基1苯酚。方法一所用乙腈溶剂虽是偶极溶剂，     

2-异丙基喹喔啉衍生物的合成及应用

以邻苯二胺化合物和α-溴代酮类化合物为原料,经过串联环化反应合成喹喔啉类化合物。部分未知的喹喔啉衍生物经过质谱和核磁分析加以确证。同时研究了2-异丙基喹喔啉在过渡金属Ag参与下的sp3C—H键硝化反应。     

辉光放电电解降解水体中阳离子桃红FG的机理

用辉光放电电解（GDE）技术对模拟染料废水阳离子桃红FG的降解过程进行了研究。通过发射光谱法测定了GDE产生的活性粒子,用紫外光谱和总有机碳（TOC）分析仪研究了不同放电时间下的脱色率和去除率,用电导率仪和酸度计测定了降解过程中溶液的电导率和pH的变化,同时用离子色谱对降解中间产物进行了分析。结合各种分析结果,探讨了GDE降解阳离子桃红FG的机理。结果表明,在最佳电压600 V时,溶液中产生HO·、O·、H·等高活性粒子;放电120 min时,200 ml 20 mg/L阳离子桃红FG的脱色率和TOC去除率分别可达99.0%和72.6%;降解液pH先减小后增大,电导率存在先增大后减小的趋势;离子色谱测试表明,降解过程中产生多种有机小分子酸。羟基自由基（HO·）对阳离子桃红FG的降解起关键作用,GDE降解阳离子桃红FG的机理为：HO·作用下助色基团键断裂,产生酚类等中间产物,然后继续被降解为醌和小分子有机酸,最终矿化为Cl^-、NO₃^-、CO₂和H₂O。     

Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms

Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has recently emerged as a potential cytotoxic agent in addition to its ameliorative activity in chemotherapy-associated side effects. In this work, the potential interactions of CBD with docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN), and 7-ethyl-10-hydroxycamptothecin (SN−38) were explored in MCF7 breast adenocarcinoma cells using different synergy quantification models. The apoptotic profiles of MCF7 cells after the treatments were assessed via flow cytometry. The molecular mechanisms of CBD and the most promising combinations were investigated via label-free quantification proteomics. A strong synergy was observed across all synergy models at different molar ratios of CBD in combination with SN−38 and VIN. Intriguingly, synergy was observed for CBD with all chemotherapeutic drugs at a molar ratio of 636:1 in almost all synergy models. However, discording synergy trends warranted the validation of the selected combinations against different models. Enhanced apoptosis was observed for all synergistic CBD combinations compared to monotherapies or negative controls. A shotgun proteomics study highlighted 121 dysregulated proteins in CBD-treated MCF7 cells compared to the negative controls. We reported the inhibition of topoisomerase II β and α, cullin 1, V-type proton ATPase, and CDK-6 in CBD-treated MCF7 cells for the first time as additional cytotoxic mechanisms of CBD, alongside sabotaged energy production and reduced mitochondrial translation. We observed 91 significantly dysregulated proteins in MCF7 cells treated with the synergistic combination of CBD with SN−38 (CSN−38), compared to the monotherapies. Regulation of telomerase, cell cycle, topoisomerase I, EGFR1, protein metabolism, TP53 regulation of DNA repair, death receptor signalling, and RHO GTPase signalling pathways contributed to the proteome-wide synergistic molecular mechanisms of CSN−38. In conclusion, we identified significant synergistic interactions between CBD and the five important chemotherapeutic drugs and the key molecular pathways of CBD and its synergistic combination with SN−38 in MCF7 cells. Further in vivo and clinical studies are warranted to evaluate the implementation of CBD-based synergistic adjuvant therapies for breast cancer.     

Interphases in the Adhesive Bonding of Fluoropolymers

Strong and durable adhesive bonds may be made between polytetrafluoroethylene (PTFE) and either cyanoacrylate (CA) or epoxy adhesives, if the PTFE surface is modified by the use of a “primer” such as triphenylphosphine (TPP) or diaminodiphenylmethane (DDM). The primer mixes with the PTFE surface, and the modified surface is then capable of forming an interphase, tens to hundreds of nanometers thick, where interpenetration of the adhesive and adherend occurs. Using CA adhesives, PTFE/CA/PTFE block compression shear bond strength (ASTM D4501-85) of over 10 MPa can be achieved, with failure occurring cohesively. Initial work with epoxy adhesives indicates that the use of DDM primer gives adhesive bonds comparable in strength with those produced by modification of the fluoropolymer surface by sodium naphthalenide.     

The Influence of Glow and Afterglow Cold Plasma Treatment on Biochemistry,Morphology, and Physiology of Wheat Seeds

Cold plasma (CP) technology is a technique used to change chemical and morphological characteristics of the surface of various materials. It is a newly emerging technology in agriculture used for seed treatment with the potential of improving seed germination and yield of crops. Wheat seeds were treated with glow (direct) or afterglow (indirect) low-pressure radio-frequency oxygen plasma. Chemical characteristics of the seed surface were evaluated by XPS and FTIR analysis, changes in the morphology of the seed pericarp were analysed by SEM and AFM, and physiological characteristics of the seedlings were determined by germination tests, growth studies, and the evaluation of α-amylase activity. Changes in seed wettability were also studied, mainly in correlation with functionalization of the seed surface and oxidation of lipid molecules. Only prolonged direct CP treatment resulted in altered morphology of the seed pericarp and increased its roughness. The degree of functionalization is more evident in direct compared to indirect CP treatment. CP treatment slowed the germination of seedlings, decreased the activity of α-amylase in seeds after imbibition, and affected the root system of seedlings.     

正反向同时引发ATRP制备凹凸棒土/聚苯乙烯杂化粒子

通过脱醇法在凹凸棒土（ATP）表面接枝γ-氨丙基三乙氧基硅烷（APTES）实现氨基化（ATP-APTES）,再经酰胺化反应接枝α-溴代异丁酰溴,从而在ATP表面固载ATRP引发基团（ATP-Br）;最后以2,2-偶氮二异丁腈（AIBN）和ATP-Br为双组分引发体系进行正反向同时引发原子转移自由基聚合（SR&NI ATRP）制备ATP接枝聚苯乙烯杂化粒子（ATP@PS）。结果表明AIBN结合ATP-Br引发体系进行SR&NI ATRP具有活性/可控聚合的特征,随催化剂用量增大,体系过早偏离一级动力学行为。聚合温度在80℃,投料比为单体/催化剂/AIBN/ATP-Br=200/0.3/0.05/0.5的条件下,接枝聚合物和游离聚合物分子量差异随转化率（c）增大逐渐增加,转化率为31.1%时,两者分子量分布（PDI）均保持在1.54以下,ATP-Br表面ATRP引发基团的引发效率为6.3%。杂化粒子在PS基体中分散得到明显改善。     

Effects of Two Distinct Psychoactive Microbes,Lacticaseibacillus rhamnosus JB-1 and Limosilactobacillus reuteri 6475, on Circulating and Hippocampal mRNA in Male Mice

Discovery of the microbiota-gut–brain axis has led to proposed microbe-based therapeutic strategies in mental health, including the use of mood-altering bacterial species, termed psychobiotics. However, we still have limited understanding of the key signaling pathways engaged by specific organisms in modulating brain function, and evidence suggests that bacteria with broadly similar neuroactive and immunomodulatory actions can drive different behavioral outcomes. We sought to identify pathways distinguishing two psychoactive bacterial strains that seemingly engage similar gut–brain signaling pathways but have distinct effects on behaviour. We used RNAseq to identify mRNAs differentially expressed in the blood and hippocampus of mice following Lacticaseibacillus rhamnosus JB-1, and Limosilactobacillus reuteri 6475 treatment and performed Gene Set Enrichment Analysis (GSEA) to identify enrichment in pathway activity. L. rhamnosus, but not L. reuteri treatment altered several pathways in the blood and hippocampus, and the rhamnosus could be clearly distinguished based on mRNA profile. In particular, L. rhamnosus treatment modulated the activity of interferon signaling, JAK/STAT, and TNF-alpha via NF-KB pathways. Our results highlight that psychobiotics can induce complex changes in host gene expression, andin understanding these changes, we may help fine-tune selection of psychobiotics for treating mood disorders.     

Effects of Three Different Doses of Inter-Alpha Inhibitor Proteins on Severe Hypoxia–Ischemia-Related Brain Injury in Neonatal Rats

Hypoxia–ischemia (HI)-related brain injury is an important cause of morbidity and long-standing disability in newborns. We have previously shown that human plasma-derived inter-alpha inhibitor proteins (hIAIPs) attenuate HI-related brain injury in neonatal rats. The optimal dose of hIAIPs for their neuroprotective effects and improvement in behavioral outcomes remains to be determined. We examined the efficacy of 30, 60, or 90 mg/kg of hIAIPs administered to neonatal rats after exposure to HI for 2 h. Postnatal day 7 (P7) Wistar rats were exposed to either sham-surgery or unilateral HI (right carotid artery ligation, 2 h of 8% O₂) brain injury. A placebo, 30, 60, or 90 mg/kg of hIAIPs were injected intraperitoneally at 0, 24 and 48 h after HI (n = 9–10/sex). We carried out the following behavioral analyses: P8 (righting reflex), P9 (negative geotaxis) and P10 (open-field task). Rats were humanely killed on P10 and their brains were stained with cresyl violet. Male extension/contraction responses and female righting reflex times were higher in the HI placebo groups than the sham groups. Female open-field exploration was lower in the HI placebo group than the sham group. hIAIPs attenuated these behavioral deficits. However, the magnitude of the responses did not vary by hIAIP dose. hIAIPs reduced male brain infarct volumes in a manner that correlated with improved behavioral outcomes. Increasing the hIAIP dose from 30 to 90 mg/kg did not further accentuate the hIAIP-related decreases in infarct volumes. We conclude that larger doses of hIAIPs did not provide additional benefits over the 30 mg/kg dose for behavior tasks or reductions in infarct volumes in neonatal rats after exposure to severe HI.     

小胶质细胞对阿尔兹海默病发生发展的影响作用

阿尔兹海默病(老年性痴呆,AD)是由β淀粉样蛋白(Aβ)和微管相关蛋白(Tau)聚集形成的具有毒性作用的寡聚物而引起的老年人主要以记忆力下降和脑部形成老年斑、神经纤维缠绕为特征的神经退行性疾病. 小胶质细胞作为中枢神经系统中的固有免疫细胞,是脑内免疫监视的关键成分,发挥内源性免疫防御作用. 正常生理状态的小胶质细胞能有效吞噬和清除毒性Aβ寡聚体,阻止AD发生. 在AD病理过程中,过度激活的小胶质细胞通过补体依赖途径过度吞噬突触,导致突触丧失,同时大量释放炎症因子,促进Tau相关病理变化,对神经元造成直接损伤,导致认知功能下降. 由此可见,小胶质细胞在AD发生发展过程中起着双刃剑的作用,探明小胶质细胞的极化状态及其在AD疾病机理中的作用将为攻克AD的药物研发提供突破性思路.     

Anti-Inflammatory Therapeutic Approaches to Prevent or Delay Post-Traumatic Osteoarthritis (PTOA) of the Knee Joint with a Focus on Sustained Delivery Approaches

Inflammation plays a central role in the pathogenesis of knee PTOA after knee trauma. While a comprehensive therapy capable of preventing or delaying post-traumatic osteoarthritis (PTOA) progression after knee joint injury does not yet clinically exist, current literature suggests that certain aspects of early post-traumatic pathology of the knee joint may be prevented or delayed by anti-inflammatory therapeutic interventions. We discuss multifaceted therapeutic approaches that may be capable of effectively reducing the continuous cycle of inflammation and concomitant processes that lead to cartilage degradation as well as those that can simultaneously promote intrinsic repair processes. Within this context, we focus on early disease prevention, the optimal timeframe of treatment and possible long-lasting sustained delivery local modes of treatments that could prevent knee joint-associated PTOA symptoms. Specifically, we identify anti-inflammatory candidates that are not only anti-inflammatory but also anti-degenerative, anti-apoptotic and pro-regenerative.