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Antiinflammatory and Antiproliferative Activity of Naphthoxazole, Fused Hetero-benzoxazole and Bridged Benzobicyclic Photoproducts 萘恶唑、杂苯并恶唑和桥联苯并双环光产物的抗炎和抗增殖活性
IF 0.3 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2019-07-24 DOI: 10.5562/cca3530
Ivana Šagud, A. Ratković, Matea Cedilak, M. Bosnar, Vanja Kelava, I. Škorić
Biological activity of naphthoxazoles, fused hetero-benzoxazoles and benzobicyclo[3.2.1]-derivatives was investigated in proliferation and inflammation based assays. The tested compounds were prepared by photocylization or photocycloaddition reactions. Effect of compounds on proliferation of several cancer cell lines was determined by measuring cell metabolic activity through time. Lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells (PBMC) was used to investigate antiinflammatory properties of the compounds. Several naphthoxazoles and fused hetero-benzoxazoles inhibited TNFα protein expression in LPS stimulated PBMC, indicating possible antiinflammatory role which would be interesting to further investigate. Physico-chemical properties of tested compounds have been also studied using chromatographic lipophilicity measure, chrom logD and logP was calculated as the importance of physico-chemical properties of compounds at early stage of discovery of new drugs is well established. The similarities in structure and activity of some representative compounds affirm the need to further address their antiinflammatory properties.
萘恶唑、稠合杂苯并恶唑和苯并双环[3.2.1]-衍生物的生物活性在基于增殖和炎症的测定中进行了研究。测试的化合物通过光环化或光环加成反应制备。通过测量随时间变化的细胞代谢活性来确定化合物对几种癌症细胞系增殖的影响。采用脂多糖(LPS)刺激外周血单个核细胞(PBMC)的方法研究了化合物的抗炎特性。几种萘恶唑和稠合杂苯并恶唑抑制LPS刺激的PBMC中TNFα蛋白的表达,表明其可能具有抗炎作用,这将是值得进一步研究的。还使用色谱亲脂性测量方法研究了受试化合物的理化性质,计算了chrom-logD和logP,因为化合物的理化学性质在新药发现的早期阶段的重要性已经确立。一些具有代表性的化合物在结构和活性上的相似性证实了进一步解决其抗炎特性的必要性。
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引用次数: 0
Crystal Structures of the Single PDZ Domains from GRASP65 and their Interaction with the Golgin GM130 GRASP65单PDZ结构域的晶体结构及其和Golgin GM130的相互作用
IF 0.3 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2019-04-24 DOI: 10.5562/CCA3341
C. M. Jurk, Y. Roske, U. Heinemann
Among the major components of the Golgi apparatus are the GRASP family proteins, including GRASP65 on the cis-Golgi side. With its GRASP domain, GRASP65 is involved in Golgi stacking and ribbon formation. Interaction of GRASP65 with the Golgi marker protein GM130 is important for the docking of vesicles to the Golgi membrane. We present here structures of the two individual PDZ domains comprising the GRASP domain in human GRASP65. We use isothermal titration calorimetry to probe the interaction between GRASP65 and GM130. Additionally, we present evidence for the limited sequence conservation of the PDZ fold by describing the PDZ domain structure of the GRASP65 homolog Grh1 from Saccharomyces cerevisiae.
高尔基体的主要成分是GRASP家族蛋白,包括顺式高尔基体侧的GRASP65。GRASP65具有GRASP结构域,参与高尔基体堆积和带状体形成。GRASP65与高尔基标记蛋白GM130的相互作用对于囊泡与高尔基膜的对接是重要的。我们在这里展示了包括人类GRASP65中的GRASP结构域的两个单独的PDZ结构域的结构。我们使用等温滴定量热法来探测GRASP65和GM130之间的相互作用。此外,我们通过描述酿酒酵母GRASP65同源物Grh1的PDZ结构域结构,为PDZ折叠的有限序列保守性提供了证据。
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引用次数: 4
A Rapid Microwave Induced Synthesis of Isonicotinamide Derivatives and their Antifungal Activity 微波快速合成异烟酰胺衍生物及其抗真菌活性
IF 0.3 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2019-01-28 DOI: 10.5562/CCA3527
V. Bušić, K. Vrandečić, Tamara Siber, S. Roca, D. Vikić-Topić, D. Gašo-Sokač
Ten novel isonicotinamide derivatives were prepared by quaternization reactions of isonicotinamide with methyl iodide and nine differently substituted 2 bromoacetophenones under rapid microwave irradiation of 10 minutes. The microwave preparations were significantly faster and with yields higher up to 8 times, than the preparations by conventional method. The structures of synthesized molecules were determined by one- and two dimensional NMR and IR spectroscopy, mass spectrometry and elemental analysis. Antifungal activity of all compounds was tested in two different concentrations (10 and 100 µg mL–1) against Fusarium oxysporum, Fusarium culmorum, Macrophomina phaseolina and Sclerotinia sclerotiorum in vitro. From the antifungal assay it can be seen that the most prepared compounds have moderate to weak activity against M. phaseolina and F. culmorum. A very high inhibitory rate was observed against S. sclerotiorum, 62–87.5 % in concentration of 10 µg mL–1 and 83.7–93.2 % in concentration of 100 µg mL–1.
通过异烟酰胺与甲基碘和9种不同取代的2溴丙酮的季铵化反应,在10分钟的快速微波辐射下制备了10种新的异烟酰胺衍生物。微波制剂比传统方法的制剂明显更快,产率高达8倍。通过一维和二维核磁共振、红外光谱、质谱和元素分析确定了合成分子的结构。在体外测试了所有化合物在两种不同浓度(10和100µg mL–1)下对尖孢镰刀菌、秆镰孢镰刀刀菌、相位大磷虾和核盘菌的抗真菌活性。从抗真菌测定中可以看出,大多数制备的化合物对相球孢霉和秆分枝杆菌具有中等至弱的活性。观察到对核盘菌的抑制率非常高,在10µg mL–1的浓度下为62–87.5%,在100µg mL-1的浓度中为83.7–93.2%。
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引用次数: 5
Characterization of O-demethylations and Aromatic Hydroxylations Mediated by Cytochromes P450 in the Metabolism of Flavonoid Aglycons 细胞色素P450介导的黄酮类化合物代谢中O-去甲基化和芳香羟基化的表征
IF 0.3 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2019-01-28 DOI: 10.5562/CCA3528
Goran Benković, Hrvoje Rimac, Ž. Maleš, S. Tomić, Zoran Lončar, M. Bojić
One of the most important groups of metabolic enzymes is cytochrome P450 superfamily. These enzymes are important in terms of the catalytic diversity and the large number of xenobiotics that are detoxified or activated by converting to reactive metabolites. Flavonoids are xenobiotics to which humans are exposed through diet. Data on their oxidative metabolism mediated by cytochromes P450 are limited. The aim of this study was to determine the enzymatic kinetics of O-demethylation and aromatic hydroxylation of flavonoid aglycons on recombinant cytochrome P450 enzymes and human liver microsomes systems. The study was performed on ten flavonoids, namely 3,7-dihydroxyflavone, 7-hydroxyflavone, acacetin, apigenin, flavone, galangin, kaempferol, naringenin, sakuranetin, and tangeretin using liquid chromatography coupled with mass spectrometry and UV detector. Most relevant enzyme involved in metabolism of flavonoid aglycons is CYP1A2, and its catalytic effectiveness ranges from 0.5 to 2.9 × 106 M–1 min–1. Having in mind high expression and involvement of CYP1A2 in metabolism of xenobiotics including drugs, and its intraindividual differences in expression and activity, potential of drug-flavonoid competitive interactions/inhibitions should be considered when consuming dietary supplement and foods rich in flavonoids.
细胞色素P450超家族是一类重要的代谢酶。这些酶在催化多样性和大量通过转化为反应性代谢物解毒或激活的异种生物方面是重要的。黄酮类化合物是人类通过饮食接触到的外来生物。关于细胞色素P450介导的氧化代谢的数据有限。本研究的目的是确定重组细胞色素P450酶和人肝微粒体系统中类黄酮苷元的o -去甲基化和芳香羟基化的酶动力学。采用液相色谱-质谱联用技术和紫外检测器对3,7-二羟基黄酮、7-羟基黄酮、阿卡乙素、芹菜素、黄酮、高良姜素、山奈酚、柚皮素、樱花素和橘皮素等10种黄酮类化合物进行了研究。与类黄酮苷元代谢最相关的酶是CYP1A2,其催化效能为0.5 ~ 2.9 × 106 M-1 min-1。考虑到CYP1A2在包括药物在内的外源性代谢中的高表达和参与,以及它在表达和活性上的个体差异,在食用富含类黄酮的膳食补充剂和食物时,应考虑到药物-类黄酮竞争相互作用/抑制的可能性。
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引用次数: 6
Helichrysum italicum (Roth) G. Don subsp. italicum from Herzegovina 意大利蜡菊来自黑塞哥维那的斜体字
IF 0.3 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2019-01-28 DOI: 10.5562/CCA3475
S. Talić, I. Odak, Anita Martinović Bevanda, Nikolina Crnjac, M. Paštar
The chemical composition of essential oils isolated from immortelle (Helicrysum italicum subsp. italicum) collected in Herzegovina during five different periods, was investigated by GC/MS analysis. The main compounds were a-pinene (15.7 %) and γ-curcumene (12.8 %), followed by 4,6,9-trimethyldec-8-en-3,5-dione (8.7 %), neryl acetate (6.9 %), limonene (6.4 %) and β-selinene (5.3 %). In total, 69 components were identified whose share changed over the vegetative cycle. Antioxidant activity of methanolic extracts of immortelle were determined according to DPPH (IC50 = 23–34 μg/mL) and FRAP (29 μg/mL is equivalent to 1.1‒2.2 mM Fe2+) methods. Acetylcholinesterase inhibitory potential, investigated by modified Ellman’s assay and determined as IC50 values, were 340–440 μg/mL for methanol extracts and 135 μg/mL for essential oil. Metanolic extracts showed strong antioxidant activity and potential to inhibit AChE. Essential oil possesses complex chemical composition, inhibition activity of AChE and weak antioxidant capacity.
永不朽意大利蜡菊(Helicrysum italicum subsp.)精油的化学成分。采用GC/MS分析方法对5个不同时期在黑塞哥维那采集的italicum)进行了研究。主要化合物为a-蒎烯(15.7%)和γ-姜黄烯(12.8%),其次为4,6,9-三甲基癸-8-烯-3,5-二酮(8.7%),乙酸橙酯(6.9%),柠檬烯(6.4%)和β-亚麻烯(5.3%)。总共鉴定出69个组分,它们的份额在植物周期中发生了变化。采用DPPH法(IC50 = 23 ~ 34 μg/mL)和FRAP法(29 μg/mL,相当于1.1 ~ 2.2 mM Fe2+)测定了神仙草甲醇提取物的抗氧化活性。经改良Ellman法测定,甲醇提取物的乙酰胆碱酯酶抑制电位为340 ~ 440 μg/mL,精油的抑制电位为135 μg/mL。代谢提取物具有较强的抗氧化活性和抑制AChE的潜力。精油化学成分复杂,抑制乙酰胆碱酯酶活性,抗氧化能力弱。
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引用次数: 10
Behaviour of 9-Ethyl-9H-carbazole Hydrazone Derivatives Against Oxidant Systems 9-乙基-9H-咔唑腙衍生物对抗氧化剂体系的行为
IF 0.3 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2019-01-28 DOI: 10.5562/CCA3481
Çiğdem Karaaslan, E. Ince, H. Gurer-Orhan, M. Tavakkoli, O. Firuzi, L. Saso, S. Suzen
Antioxidants are helpful in prevention of several diseases related with oxidative stress including neurodegenerative disorders. In recent studies, carbazoles were given proof of promising antioxidant activities. In this article, 9-ethyl-9H-carbazole hydrazone derivatives were synthesized, characterized and their in vitro antioxidant activity and possible cytotoxic effects were investigated. Furthermore, protective effect of the synthesized derivatives against amyloid β-induced damage in PC12 neuronal cells was examined by using MTT assay. The newly synthesized carbazoles were found to have radical scavenging activity with a varying potency both in cell-free and cell-based in vitro assays. Several compounds, especially such as 3d and 3e, 3m and 3n bearing two halogen groups on the phenyl ring, were found to have cytotoxic activity. However, their cytotoxic activities were not higher than that of melatonin. Several compounds also significantly protected neuronal PC12 cells against amyloid β-induced damage, which can be defined as neuroprotective agents. (4-(2-((9-Ethyl-9H-carbazol-3-yl)methylene)hydrazinyl)benzonitrile) 3r was found as the most active compound with both radical scavenging activity and neuroprotective effects against amyloid β-induced damage. These findings might provide an alternative strategy for developing novel carbazole derivatives for management of neurodegenerative diseases, such as Alzheimer's disease.
抗氧化剂有助于预防几种与氧化应激有关的疾病,包括神经退行性疾病。在最近的研究中,咔唑被证明具有良好的抗氧化活性。本文合成了9-乙基- 9h -咔唑腙衍生物,对其进行了表征,并对其体外抗氧化活性和可能的细胞毒性进行了研究。此外,采用MTT法检测合成的衍生物对淀粉样蛋白β诱导的PC12神经元细胞损伤的保护作用。新合成的咔唑被发现具有不同效力的自由基清除活性,无论是在无细胞和基于细胞的体外测定。一些化合物,特别是在苯环上有两个卤素基团的3d和3e, 3m和3n,被发现具有细胞毒性活性。但其细胞毒活性并不高于褪黑素。一些化合物还可以显著保护神经元PC12细胞免受淀粉样蛋白β诱导的损伤,可以定义为神经保护剂。(4-(2-((9-乙基- 9h -咔唑-3-基)亚甲基)肼基)苯腈)3r是活性最高的化合物,对淀粉样蛋白β诱导的损伤具有自由基清除活性和神经保护作用。这些发现可能为开发用于治疗神经退行性疾病(如阿尔茨海默病)的新型咔唑衍生物提供另一种策略。
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引用次数: 3
Mobility of Trace Elements in Pore Solutions of Portland Cement Pastes Exposed to Leaching 硅酸盐水泥浆体浸出后孔隙溶液中微量元素的迁移率
IF 0.3 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2019-01-28 DOI: 10.5562/CCA3511
Marija Đuroković, D. Matković-Čalogović, I. Janotka
Two Portland cement pastes, CEM I 42.5R and CEM III/A 52.5N were exposed to leaching by soft water throughout a one–year hydration period. Mobility of trace elements was investigated by determination of their pore solution concentration in the course of time. Eleven trace elements were included in this research: antimony, arsenic, cadmium, chromium, cobalt, copper, mercury, nickel, lead, vanadium and zinc. The possible usage of the pore solution trace elements concentration in monitoring of deleterious leaching reactions and prediction of environmental risk was investigated.
两种硅酸盐水泥浆体,CEM I 42.5R和CEM III/A 52.5N,在一年的水化期内暴露于软水浸出。通过测定微量元素在一段时间内的孔溶液浓度来研究微量元素的迁移率。本研究包括11种微量元素:锑、砷、镉、铬、钴、铜、汞、镍、铅、钒和锌。研究了孔隙溶液微量元素浓度在监测有害浸出反应和预测环境风险中的可能用途。
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引用次数: 3
Design, Synthesis, and Spectroscopic Study of 7-Azaindolyl Hydrazones with Anti-Breast Cancer Activity 具有抗乳腺癌活性的7-氮唑腙的设计、合成及光谱研究
IF 0.3 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2019-01-28 DOI: 10.5562/CCA3418
Sakharam B. Dongare, B. Bandgar, Pravin S. Bhale, Sadanand N. Shringare, H. Chavan
A series of 7-azaindolyl hydrazones were prepared by reacting of hydrazides of 7-azaindole-3-acetic acids with aromatic aldehydes and N-substituted indolyl-3-carboxyaldehydes. Structure of all the synthesized compounds were satisfactorily correlated by IR, 1H NMR, 13C NMR and mass spectroscopic evidences. The synthesized compounds were evaluated for their possible anticancer potential against MCF-7 induced breast carcinoma. It is worth mentioning that most of the compounds were considerably active against MCF-7 cell line with GI50 values ranging from 22.3–81.0 μM. The hydrazones of N-1-substituted indole-3-carboxyaldehydes 9f, 9g, 9h, 9c, and 9j were active against MCF-7 cell line with GI50 values less than 40 μM (GI50 = 22.3 and 24.9, 29.6, 30.2 and 37.8 μM respectively) with moderate TGI values (TGI = 56.6, 59.5, 65.5, 70.7 and 94.6 μM respectively). The active compounds were also screened against the normal Vero monkey cell line, which showed moderate selectivity against inhibition of cancer cells.
以7-氮唑-3-乙酸为原料,以芳香醛和n -取代吲哚-3-羧醛为原料,制备了一系列7-氮唑酰腙。经IR、1H NMR、13C NMR和质谱分析,所有化合物的结构均具有良好的相关性。评价了合成的化合物对MCF-7诱导的乳腺癌的潜在抗癌作用。值得一提的是,大多数化合物对MCF-7细胞株具有较强的活性,其GI50值在22.3 ~ 81.0 μM之间。n -1取代吲哚-3-羧醛9f、9g、9h、9c和9j的腙对MCF-7细胞株的GI50值小于40 μM (GI50分别为22.3和24.9、29.6、30.2和37.8 μM), TGI值适中(TGI分别为56.6、59.5、65.5、70.7和94.6 μM)。活性化合物对正常Vero猴细胞系也进行了筛选,对癌细胞的抑制表现出中等的选择性。
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引用次数: 10
Phytochemical Composition, Antiradical and Anticholinesterase Potentials of Centaurea alba and Centaurea jacea Volatile Oils 矢车菊和矢车菊挥发油的植物化学成分、抗自由基和抗胆碱酯酶活性
IF 0.3 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2019-01-28 DOI: 10.5562/CCA3458
O. Politeo, Ivana Carev, Anita Veljača
This paper reports on the phytochemical composition as well as antiradical and anticholinesterase potential of volatile oils isolated from Centaurea alba and Centaurea jacea, from Croatia. The volatile components, obtained by hydrodistillation, were determined by GC and GC-MS analyses. A total of 18 compounds were identified in C. alba volatile oil with hexadecanoic acid, germacrene D and tetradecanoic acid as main compounds. A total of 29 compounds were identified in C. jacea volatile oil, with epi-bicyclosesquiphellandrene, aromadendrene and hexadecanoic acid as a major compounds. The tested volatile oils showed low DPPH inhibition potential as well as low to moderate antiAChE potential and low antiBuChE potential.
本文报道了从克罗地亚的矢车菊和矢车菊中分离的挥发油的植物化学成分以及抗自由基和抗胆碱酯酶的潜力。通过GC和GC-MS分析测定了加氢蒸馏得到的挥发性成分。白藜芦挥发油中共鉴定出18个化合物,其中十六烷酸、锗马烯D和十四烷酸为主要化合物。在姜挥发油中共鉴定出29个化合物,其中以表双环十七碳烯、芳马德琳和十六烷酸为主要化合物。测试的挥发油显示出低DPPH抑制潜力以及低至中等抗AChE潜力和低抗BuChE潜力。
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引用次数: 11
Simulation of Alternative Differential Multi-pulse Voltammetry. Evaluation of the Electrochemical Reversibility by the Voltammogram Symmetry 交替差分多脉冲伏安法的仿真。用伏安对称评价电化学可逆性
IF 0.3 4区 化学 Q4 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2019-01-28 DOI: 10.5562/CCA3485
D. Jadreško
A theoretical analysis of reversible and kinetically controlled electrode reactions in conditions of alternative differential multi-pulse voltammetry (ADMPV) is presented. The degree of reversibility, as well as symmetry of the electron transfer reaction, can be estimated by visual inspection of the ADMP voltammogram. The values of electron transfer coefficient and the standard rate constant of a simple electrode reaction Ox + ne− ⇄ Red, can be determined from the slope of linear dependence of the peak currents ratio on the logarithm of pulse duration. The criteria for recognition of reversible and kinetically controlled electrode reactions by alternative differential multi-pulse voltammetry are given.
对交替差分多脉冲伏安法(ADMPV)条件下可逆和动力学控制的电极反应进行了理论分析。可逆性的程度,以及电子转移反应的对称性,可以通过观察ADMP伏安图来估计。简单电极反应(Ox + ne−Red)的电子传递系数和标准速率常数的值可以由峰值电流比与脉冲持续时间对数的线性关系的斜率来确定。给出了交替微分多脉冲伏安法识别可逆和动力学控制电极反应的判据。
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引用次数: 0
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Croatica Chemica Acta
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