Synthesis and antitumor activities of structure-related small molecular compounds of gambogic acid

Through simplifying the complicated skeleton of the natural product gambogic acid, two series derivatives of chromone and xanthone were synthesized and examined for their antitumor activities against several cancer cells in vitro by MTT method. The results showed that appropriate introduction of prenyl group to the small molecular compounds could elevate their antitumor activities. The structure–activities relationship of synthesized compounds certified that the bridgecore in gambogic acid was very important for keeping its antitumor activities.

STRUCTURE OF MOLECULAR COMPOUND CRYSTAL A_2B(A =1, 6, 7, 8,-TETRA-PHENYL (3, 4-BENZO)BICYCLO[4, 2, 0]OCTA-7-ENE, B=CIS, CIS-1,2,3,4,-TETRAPHENYLBUTADIENE)

C100H78, (A: C36H28, B: C28H22) Mr = 1279. 74, monoclinic, P21/a, a=17. 282(3), b=10. 669(4), c= 19, 927(3) A , β =102. 99(1)°,V = 3580. 1(2) A3, Z=2, μ(MoKα) = 0. 623cm-1, F(000) = 1356, Dc=1. 187g/cm3, room temperature. The final R=0. 084, Rw = 0. 086 for 1255 independent observed reflections (I≥3σ(I)). Owing to the existence of 1,6,7, 8-Tetraphenyl (3,4-benzo)-bicyclo[4, 2, 0]octa-7-ene(A) , cis, cts-1, 2, 3, 4-Tetraphenylbutadiene (B) in A2B can take the different conformation from the one in the pure B crystal. The reason of the formation of this molecular compound crystal is put forward.

Composition and origin of molecular compounds in the condensate oils of the Dabei gas field, Tarim Basin, NW China

The Dabei gas field in the Kuqa Depression of the Tarim Basin is the most complex and deep continental condensate gas field in China. Comprehensive two-dimensional gas chromatography?time of flight mass spectrometer (GC×GC-TOFMS) analysis was conducted on five condensate oil samples from this field. The results show that the samples have n-alkane series in complete preservation and rich adamantanes. According to the methyladamantane index, the condensate oil is the product of the source rock with vitrinite reflectance (Ro) of 1.3%–1.6%. According to the gas maturity calculated through carbon isotope and vitrinite reflectance, the natural gas is corresponding to Ro of 1.3%–1.7%, reflecting that the natural gas and condensate oil are basically formed during the same period at the high maturity stage of source rock. The Dabei gas field has favorable geological conditions for hydrocarbon accumulation: thick salt rock in the Paleogene acts as a regional high-quality caprock directly overlying the high-quality sandstone reservoir of the Cretaceous, the coal source rocks have high hydrocarbon generation intensity and provide continuous oil and gas, and the subsalt thrust structures develop in rows with rich faults, providing migration pathways for oil and gas migration. These factors together controlled the formation of the Dabei gas field.

Some Topological Values of Supramolecular Chain of Different Complexes of N-Salicylidene-L-Valine

L-valine is a glycogen-type amino acid regarded among the necessary mammalian amino acids.This is an amino acid that is essential for protein synthesis.N-salicylidene-L-valine is gaining a lot of attention because of its unique structure and increased catalytic and cytotoxic activity.We explore the chain of supramolecular dialkyltin N-salicylidene-L-valine complexes 2,3,and 4 to learn more about this structure and its features regarding topological indices.We computed the first and second Randi′c index,harmonic index,sum-connectivity index,atom-bond-connectivity index,geometric arithmetic index and reduced reciprocal Randi′c index of Supramolecular Chain of Different Complexes of N-Salicylidene-L-Valine.Furthermore,we present an analysis of such structures using specific examples,as well as a comparison of topological indices.

New developments in small molecular compounds for anti-hepatitis C virus(HCV) therapy

Infection with hepatitis C virus(HCV) affects approximately 170 million people worldwide.However,no vaccine or immunoglobulin is currently available for the prevention of HCV infection.The standard of care(SOC) involving pegylated interferon-α(PEG-IFN α) plus ribavirin(RBV) for 48 weeks results in a sustained virologic response in less than 50% of patients with chronic hepatitis C genotype 1,the most prevalent type of HCV in North America and Europe.Recently,reliable in vitro culture systems have been developed for accelerating antiviral therapy research,and many new specifically targeted antiviral therapies for hepatitis C(STAT-C) and treatment strategies are being evaluated in clinical trials.These new antiviral agents are expected to improve present treatment significantly and may potentially shorten treatment duration.The aim of this review is to summarize the current developments in new anti-HCV drugs.

The Promotion Effect of Low-Molecular Hydroxyl Compounds on the Nano-Photoelectrocatalytic Degradation of Fulvic Acid and Mechanism

A significant promotion effect of low-molecular hydroxyl compounds(LMHCs) was found in the nano-photoelectrocatalytic(NPEC) degradation of fulvic acid(FA),which is a typical kind of humic acid existing widely in natural water bodies,and its influence mechanism was proposed.A TiO_2 nanotube arrays(TNAs) material is served as the photoanode.Methanol,ethanediol,and glycerol were chosen as the representative of LMHCs in this study.The adsorption performance of organics on the surface of TNAs was investigated by using the instantaneous photocurrent value.The adsorption constants of FA,methanol,ethanediol,and glycerol were 43.44,19.32,7.00,and 1.30,respectively,which indicates that FA has the strongest adsorption property.The degradation performance of these organics and their mixture were observed in a thin-layer reactor.It shows that FA could hardly achieve exhausted mineralization alone,while LMHCs could be easily oxidized completely in the same condition.The degradation degree of FA,which is added LMHCs,improves significantly and the best promotion effect is achieved by glycerol.The promotion effect of LMHCs in the degradation of FA could be contributed to the formation of a tremendous amount of hydroxyl radicals in the NPEC process.The hydroxyl radicals could facilitate the complete degradation of both FA and its intermediate products.Among the chosen LMHCs,glycerol molecule which has three hydroxyls could generate the most hydroxyl radicals and contribute the best effective promotion.This work provides a new way to promote the NPEC degradation of FA and a direction to remove humus from polluted water.

An Innovative Method for the Determination of Sulfur-containing Compounds by Vapor Molecular Absorption Spectrometry

Since the most sensitive resonance lines of nonmetallic elements are situated in vacuum ultraviolet region （below 190 nm）, they can not be directly determined with a common AAS instrument covering the spectral range from 190 to 700 nm. The molecular absorption spectrometry is often used for the determination of nonmetallic elements. Syty et al. used vapor molecular absorption spectrometry（VMAS） to determine the sulfur dioxide and sulfide, in which a hydrogen hollow cathode lamp was used as a continuum source to determine SO;at 210 nm and a deuterium arc

Magnetic Properties and Molecular Field Analysis of (Ce,Nd)_2(Fe,Si,Mn)_(17) Compounds

The temperature dependent magnetization of the (Ce,Nd) 2(Fe,Si,Mn) 17 intermetallic compounds were measured and analyzed by molecular field theory (MFT). The relationship between T C and the intrasublattice coupling interactions was discussed. The two sublattice MFT model can well describe the temperature dependence of the magnetization for all the compounds investigated. Ce ion in (Ce,Nd) 2Fe 17 compounds does not simply dilute the magnetic structure, but is likely present in a mixed valence state. The substitution of Si for Fe strongly raises T C and the mean Fe moment remains unchanged for Ce 2(Si,Fe) 17 compounds, and the 3d exchange coupling constant J FF increases linearly. Mn decreases T C of Nd 2(Mn, Fe) 17 compound by reducing J FF .

Influence of Molecular Structure on the Dimerization Reactivity of Germaaromatic Compounds: a Theoretical Study

Density functional theory （DFT） calculations, at the B3LYP/6-311G＊＊ level of theory, were performed to study the reaction mechanism and potenti4the potential energy surface of the studied reactions was investigated. Our calculation results show that [2 ＋ 2] and [4 ＋ 4] reactions are concerted and synchronous processes; while [4 ＋ 2] reactions proceed via a concerted but asynchronous way in general. [2 ＋ 2] and [4 ＋ 2] reactions of germabenzenes and 1-germana- phthalene proceed much more easily than the corresponding [4 ＋ 4] reaction, both thermo- dynamically and kinetically; while most [4 ＋ 2] paths have lower activation barrier than the corres- ponding [2 ＋ 2] ones. As the number of six-membered aromatic rings in reactant molecules becomes larger, [2 ＋ 2], [4 ＋ 2] and [4 ＋ 4] reactions become easier to proceed. The influence of substituents at the Ge atom of germabenzenes on the potential energy surface of [2 ＋ 2] and [4 ＋ 2] reactions correlates with their electronic properties and volume. Solvent effect is not crucial for the potential energy surfaces of the studied reactions.

Molecular Simulation Studies on Basicity of Nitrogen-containing Compounds

The DFT-based(density functional theory) ab initio quantum mechanical methods have been applied to study the basicity of the nitrogen-containing compounds in petroleum.The results have indicated that there is a distinct relationship between the protonation energy of nitrogen-containing compounds and their basicity.The more negative the protonation energy,the stronger the basicity is.It has been also found that aliphatic amines are more basic than pyridines or aromatic amines,and all these compounds are more basic than pyrroles.The addition of the aromatic rings can influence the basicity of anilines,while the 5- and 6-membered heterocyclic compounds function differently.The solvent properties may affect the basicity of these nitrogen-containing compounds.

Target Prediction and Molecular Mechanism of Compound Honggencao for Upper Respiratory Tract Infection Based on Network Pharmacology

Objective: The target prediction and molecular mechanism of compound Honggencao in the treatment of upper respiratory tract infection were investigated based on network pharmacology. Methods: In the database of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, chemical composition and potential targets of compound Honggencao were mined, and the target gene of upper respiratory tract infection of compound Honggencao was extracted from GeneCards databases. The protein-protein interaction of target genes was constructed. Then, the essential genes of enrichment of KEGG pathway analysis and functional analysis were analysed. Results: Compound Honggencao had 69 kinds of active ingredients. The upper respiratory tract infection of the target gene was 186 that built compound Honggencao on the relationship between upper respiratory tract infections of protein interaction networks, which had a total of 186 nodes, 3515 sides. Fifty-six essential genes were including IL-17, EGFR and CDND1, and so on. Gene ontology analysis had 2567 items, and pathway analysis was 166 items. The main signaling pathways involved with IL-17 signaling pathways, tumour necrosis factor signal pathway and human cytomegalovirus infection, and so on. Conclusion: The pharmacological action of compound Honggencao on upper respiratory tract infection was characterized by the synergistic effect of multiple components and multiple targets, which provided an absolute theoretical basis for the research on the pharmacological direction of molecular signaling pathway and a specific theoretical basis for clinical use.

猴头菌培养液乙酸乙酯提取物的化学成分研究

目的研究猴头菌培养液乙酸乙酯提取物的化学成分。方法通过凝胶柱色谱、硅胶柱色谱、半制备高效液相色谱等技术进行分离和纯化;根据其理化性质数理和波谱对得到的化合物进行结构鉴定。结果从猴头菌培养液乙酸乙酯提取物中分离并鉴定得到22个化合物,分别为3-甲氧基-4-羟基苯甲醛(1),吲哚甲酸甲酯(2),2-呋喃甲酸(3),苯甲酸(4),2(3H)-苯并恶唑酮(5),香草酸(6),没食子酸(7),polisin C(8),bis(2-ethylhexyl)benzene-1,2-dicarboylate(9),p-tyrosyl acetate(4-hydroxyphenethyl acetate)(10),1-(4-hydroxy-3,5-dimethoxyphenyl)ethanon(11),对羟基苯乙酮(12),1-苯基-1,2-丙二醇(13),6-羟基异苯并呋喃-1(3H)-酮(14),对羟基苯乙醛(15),1H-吲哚-3-吡咯甲醛(16),环(脯氨酸-缬氨酸)(17),环(脯氨酸-亮氨酸)(18),环(苯丙氨酸-缬氨酸)(19),环(异亮氨酸-苯丙氨酸)(20),苜蓿素(21),dihydro-4-hydroxy-2(3H)-furanone(22)。结论除化合物16和21外,其他化合物均为首次从猴头菌培养液中分离得到。

基于网络药理学和生物信息学探讨满药复方木鸡颗粒治疗肝癌的分子机制

利用网络药理学和生物信息学方法揭示复方木鸡颗粒治疗肝癌的作用机制。通过TCMSP、Swiss Target Prediction数据库分别获取复方木鸡颗粒的活性成分以及相关靶点;在GEO数据库筛选肝癌的相关靶点;利用Venny 2.1在线平台获取药物与疾病的共同靶点;由Cytoscape 3.8.2绘制药物–成分–靶点–疾病网络;用STRING数据库构建PPI网络;通过DAVID数据库进行GO功能富集和KEGG通路富集分析;利用Kaplan Meier-Plotter数据库对关键基因的表达量及预后关联性进行分析;运用AutoDock软件对关键成分和靶点进行分子对接验证。复方木鸡颗粒中共获得37个活性成分,筛选出57个共有靶点,涉及生物过程98条、细胞成分17条、分子功能37条,介导15条信号通路。生存期分析结果显示,ESR1、CYP3A4、G6PD基因的表达量与肝癌患者的生存期具有相关性。分子对接表明筛选的6个活性成分与6个关键靶点蛋白之间具有较好的结合能力。复方木鸡颗粒中的大豆皂苷C、柚皮素、β-谷固醇、汉黄芩素等活性成分可以作用于ESR1、CYP3A4、G6PD等靶点,可能通过P53、戊糖磷酸途径、MAPK等信号通路发挥治疗肝癌的作用。

基于网络药理学探讨栀黄止痛散治疗类风湿性关节炎作用机制及实验验证

目的结合网络药理学及体外细胞实验探索栀黄止痛散(Zhi-Huang-Zhi-Tong powder,ZHZTP)治疗类风湿性关节炎(rheumatoid arthritis,RA)的有效物质基础及相关作用机制。方法使用数据库检索并筛选得到ZHZTP活性成分靶点和疾病靶点;交集得到共同靶点;构建“药物-成分-靶点”关系网络图对交集基因进行GO和KEGG富集分析;并将核心成分与核心靶点进行分子对接。最后基于HUVEC细胞体外炎症模型,采用MTT法、平板划痕实验及蛋白质印迹等方法验证ZHZTP的药效及机制。结果ZHZTP中筛选出核心成分熊果酸和大黄素;治疗RA的重要靶点AKT1、IL-6和TNF;富集分析中,GO结果表明,ZHZTP对细胞分子功能、生物学功能及细胞组成均有影响,KEGG结果表明,ZHZTP的功能主要富集在PI3K-AKT、TNF和IL-17信号通路;分子对接结果显示,核心成分与核心靶点具有较好结合作用。体外结果表明,不同浓度的ZHZTP均可抑制HUVECs的炎性增殖和迁移,并且能够抑制PI3K,AKT及m-TOR蛋白表达水平。结论ZHZTP可能通过PI3K/AKT/m-TOR信号通路调控RA疾病发展进程,从而发挥抗RA作用,其主要有效物质基础为熊果酸和大黄素。

吐根碱通过GLP-1R促进大鼠胰岛组织胰岛素分泌作用的研究

目的探讨吐根碱通过胰高血糖素样肽-1受体(glucagon-like peptide-1 receptor,GLP-1R)促进离体大鼠胰岛组织胰岛素分泌作用。方法分离大鼠胰岛组织进行胰岛素分泌实验,根据实验设计使用不同浓度的吐根碱(2、10、50μmol·L^(-1))、不同浓度葡萄糖(2.8、11.1、16.7 mmol·L^(-1))以及特异性GLP-1R拮抗剂Exendin(9-39)孵育胰岛组织。酶联放射免疫的检测方法测定每组上清液胰岛素分泌量。使用SYBYL-X2.0软件将小分子化合物与GLP-1R(PDB代码:5NX2)进行对接。结果胰岛素分泌实验结果显示在高糖(11.1 mmol·L^(-1))条件下,胰岛素分泌量在吐根碱作用下明显升高,且具有剂量依赖性。低糖(2.8 mmol·L^(-1))条件下,胰岛素分泌量在吐根碱干预下没有明显变化,但在高糖(11.1、16.7 mmol·L^(-1))条件下,胰岛素分泌量在吐根碱作用下明显升高,具有类似GLP-1R激动剂葡萄糖浓度依赖性促胰岛素分泌特点。吐根碱与GLP-1R对接打分是Total Score=6.82,C Score=5,表明吐根碱与GLP-1R有良好的亲和力。当GLP-1R被Exendin(9-39)阻断后,吐根碱促胰岛素分泌作用明显降低。结论吐根碱通过激活GLP-1R发挥促离体大鼠胰岛组织胰岛素分泌作用。

带功能手柄的二苯并呫吨类染料(EC5)用于生物成像

短波红外光谱区(大于800 nm)的荧光团目前广泛用于生物医学领域,理想的染料应明亮、光化学稳定性高、生物相容性好并且易于衍生以便引入功能性基团。开发了一种具有双可修饰位点的二苯并呫吨类近红外荧光染料EC5,可用于荧光成像。以7-溴-2-萘酚为起始原料,通过高效的5步级联反应得到EC5,并由核磁共振氢谱、碳谱、高分辨质谱及X射线衍射鉴定。EC5在二氯甲烷中最大吸收和发射波长分别为871 nm和923 nm,荧光亮度高达38715,荧光寿命为0.70 ns。同时测试了EC5在极性溶剂中的聚集性、光化学稳定性,结果表明:EC5即使高达100μmol/L也不会出现聚集现象,高功率880 nm激光持续照射仍能保持吸光度几乎不变,同时高浓度生物活性物质亦不会使EC5染料降解,说明其具有优异的抗聚集性、抗光漂白能力及化学稳定性。最后使用EC5对BALB/c小鼠进行了高时空分辨的荧光成像以及防伪书写,说明EC5在近红外荧光活体成像领域具有广泛的应用前景。

超临界萃取结合分子蒸馏纯化生姜精油及其挥发性成分分析

为研究超临界萃取结合分子蒸馏纯化生姜精油的最佳工艺参数,鉴定生姜精油的挥发性成分,以舒城黄姜为原料,通过单因素试验和正交试验优化了超临界CO_(2)流体萃取(supercritical CO_(2)fluid extraction,SFE)生姜油的最佳工艺条件,考察了分子蒸馏(molecular distillation,MD)温度对分离纯化生姜精油效果的影响,并通过气相色谱-质谱联用对生姜精油的挥发性成分进行了分析。结果表明,超临界CO_(2)流体萃取结合分子蒸馏(SFE-MD)纯化生姜精油的最佳工艺条件为萃取压力24 MPa、萃取温度45℃、萃取时间2 h、分子蒸馏温度80℃,在此条件下,生姜精油的综合得率为2.53%,显著高于水蒸气蒸馏精油得率0.96%(P<0.05)。挥发性成分分析显示,α-姜烯、β-倍半水芹烯、β-红没药烯是生姜精油的主要挥发性成分,百分含量达70%以上,其中α-姜烯百分含量为42.13%,高于水蒸气蒸馏生姜精油α-姜烯百分含量40.59%。该方法绿色环保,萃取率高,精油品质好,为生姜精油的进一步研究开发提供参考。

基于网络药理学和分子对接探讨天花粉治疗肺癌的作用机制

目的基于网络药理学和分子对接的方法探讨天花粉治疗肺癌的作用靶点及机制。方法检索时限为建库至2022年7月。采用中药系统药理学数据库和分析平台(TCMSP)、中医药综合数据库(TCMID)结合PubChem数据库相关文献筛选出天花粉的活性成分,通过TCMSP、TCMID、SwissTargetPrediction数据库获取活性成分的潜在靶点;检索GeneCards、人类孟德尔遗传综合数据库(OMIM)、TTD、DrugBank数据库收集肺癌疾病靶点;利用线上网站Venny 2.1将药物与疾病靶点取交集并绘制韦恩图;应用String数据库绘制交集靶点的蛋白互作网络;使用Cytoscape 3.8.2软件构建“药物-活性成分-疾病-靶点”网络图;运用Metascape数据库对共同靶点进行基因本体(GO)富集化分析和京都基因和基因组数据库(KEGG)通路富集分析;采用Autodock软件进行分子对接验证。结果天花粉通过筛选得到活性成分28种,201个作用靶点;检索4大疾病数据库共获取肺癌靶点1645个;药物与疾病共有37个交集靶点;根据连接度(degree)值大小,确定雌激素受体1(ER1)、信号转导和转录激活因子3(STAT3)、表皮生长因子受体(EGFR)为核心靶点。GO富集分析发现天花粉可能通过调节腺体发育、细胞增殖、细胞黏附、酶、受体、蛋白质的活性等治疗肺癌。KEGG通路富集分析显示天花粉可能作用于化学致癌受体激活、癌症通路、缺氧诱导因子1(HIF-1)信号通路、癌症中的微RNA、蛋白聚糖等发挥作用。分子对接结果显示,关键小分子化合物与核心靶点的结合活性显著。结论天花粉通过多靶点、多通路机制发挥治疗肺癌的作用,为后续实验和临床应用奠定基础。

SEBS与常用单质炸药的相容性研究

将分子动力学(MD)模拟方法中理论键长变化趋势与差示扫描量热法(DSC)测得的分解温度变化情况相结合,分析了热塑性弹性体氢化苯乙烯-丁二烯-苯乙烯嵌段共聚物(SEBS)与推进剂中常用的单质炸药黑索今(RDX)、奥克托今(HMX)、六硝基六氮杂异伍兹烷(CL-20)之间的相容性。MD模拟结果表明:RDX、HMX、CL-20与SEBS共混体系的引发键最大键长随温度的升高而增加,与单质炸药单组分体系相比均没有明显的变化,推测SEBS与RDX、HMX、CL-20共混后稳定性较好,不易发生引发键的断裂。DSC结果中,RDX、HMX、CL-20与SEBS共混后,热分解温度变化均在3℃以内,表明SEBS与RDX、HMX和CL-20之间相容性好。进一步,选择相容性差的二号中定剂(C_(2))和3,4-二硝基呋咱基氧化呋咱(DNTF)作为对照体系,进行MD模拟和DSC分析发现,引发键最大键长明显增加,DSC热分解温度提前了70℃以上,验证了引发键键长预测相容性优劣的可行性。