金属组学和金属蛋白质组学技术于生物医药研究的应用

金属是生命过程中必不可少的辅助因子,是许多关键细胞进程中的必需元素。金属组学作为一门新兴的研究领域,旨在了解并揭示基于金属的生命过程的分子机制及金属的生物活性,相关研究在近年来得以蓬勃发展并受到广泛关注。本文详述了金属组学的概念及相关研究技术,重点介绍金属组学的一个重要研究分支——金属蛋白质组学,并对该领域应用于生物医药研究取得的进展进行综述,内容涵盖金属/金属药物在单细胞层面的摄取研究,组织和器官中的金属/金属药物分布研究、及其在细胞内结合靶点蛋白的鉴定及表征,金属蛋白的生物信息学分析等方面。基于以上研究现状,进一步探讨了金属组学技术在生物医药研究中所面临的挑战及发展前景。     

吖啶类化合物在抗肿瘤方面的研究进展

吖啶类衍生物是一类含氮的有机杂环化合物,由于其在抗炎、抗菌及抗肿瘤方面体现了较好的生物活性而受到了广泛关注。本文对近年来吖啶类化合物在抗肿瘤方面的国内外研究成果进行了综述,对其主要作用靶点如端粒酶、拓扑异构酶Ⅰ/Ⅱ、微管蛋白、ABCG2/ P-glycoprotein (P-gP)以及蛋白激酶等方面的研究进行了介绍,并指出该类化合物的发展方向及应用前景。     

钒-药物分子配合物生物活性研究进展

无机钒化合物具有降血糖、抗癌、抗炎和抗菌等作用,但生物利用度低,且有一定的毒性,影响了其在药物领域的应用。选择药物分子作为钒的配体,不仅可提高钒化合物的生物利用度,而且可增强或改进药物分子的活性,同时可能降低钒的毒性,从而成为近年来钒化学领域一个新的研究方向。本文主要介绍钒与不同类型药物分子形成配合物的生物活性及相关工作。     

一氧化氮供体化合物的合成方法研究进展

一氧化氮(NO)作为生物信使或效应分子在体内发挥重要的生理作用,因其具有多种多样的生物活性在临床应用方面得到广泛关注.体内NO生成不足常与多种疾病的形成密切相关,NO供体化合物可以通过在体内释放NO治疗和预防多种疾病.随着NO供体化合物的广泛应用,其合成方法引起了国内外研究人员的高度重视.结合国内外学者对这方面的研究,对近10年NO供体化合物的合成方法研究进展进行综述.     

钒化合物药用研究前景展望

本文针对钒化合物在药用研究中的挑战,结合国内外在相关领域的主要进展,从其作用机制的化学基础出发,分析了钒化合物可能的作用物种以及钒化合物所诱导产生的活性氧物种在其生物效应中的作用;同时,从疾病之间的相互联系,探讨了如何有效利用钒化合物生物效应的特点,并进一步指出钒化合物在药用研究中的前景及未来的研究策略.     

基于气相色谱-质谱和网络药理学探讨紫斑罂粟壳挥发油镇咳祛痰平喘的作用机制

为研究紫斑罂粟壳挥发油镇咳化痰平喘的活性成分及作用机制,采用气相色谱-质谱（GC-MS)联用法分析罂粟壳挥发油成分,并结合Pubchem和Swiss Target Prediction数据库筛选活性成分靶点. 其中,在GeneCards数据库中检索镇咳、祛痰、平喘相关的靶点,利用在线Venn取交集基因,Cytoscap 3.7.1软件构建成分-靶点-疾病网络图筛选关键成分,String数据库构建蛋白互作网络筛选核心作用靶点,DAVID数据库进行GO功能和KEGG通路富集分析. 结果表明,GC-MS鉴别出紫斑罂粟壳挥发油中28个化学成分,虚拟筛选获得20个活性成分对应的259个靶点. 网络药理学预测紫斑罂粟壳挥发油通过肿瘤坏死因子（TNF）、磷酸化蛋白激酶（AKT1）、SRC蛋白激酶（SRC）、表皮生长因子受体（EGFR）和丝裂原活化蛋白激酶 1（MAPK1）等关键靶点,进而协同调控肿瘤通路,神经配体-受体相互作用、PI3K-Akt信号通路等多条信号通路发挥镇咳祛痰、平喘的治疗作用. 研究为后续试验研究罂粟壳挥发油的药效物质及作用机制提供参考.     

基于多靶点分子对接筛选金银花治疗非酒精性脂肪肝成分研究

整合多靶点分子对接和反向靶点预测技术探究金银花治疗非酒精性脂肪肝(NAFLD)物质基础及潜在机制。借助TCMSP、ETCM数据库并挖掘文献收集金银花成分,以PPARα、PPARδ及FXR受体为靶标,运用分子对接筛选金银花中活性化合物,反向靶点预测活性化合物潜在靶点,构建蛋白互作网络并进行生物功能和通路富集。11种金银花活性成分对3个靶标的亲和力高于阳性对照,野漆树苷与PPARα的结合能力最强,3,5-二-O-咖啡酰奎宁酸甲酯与PPARδ和FXR结合能力最强。初步获得金银花治疗NAFLD主要成分为黄酮类和酚酸类,其中野漆树苷、3,4-二-O-咖啡酰奎宁酸甲酯、3,5-二-O-咖啡酰奎宁酸甲酯、异绿原酸B发挥主要作用。筛选出的成分主要通过PI3K-Akt、MAPK和胰岛素信号通路特异地作用于肝、脂肪细胞和肝癌细胞发挥治疗NAFLD的作用。本研究基于多靶点分子对接技术筛选金银花治疗NAFLD活性成分,提示金银花酚酸类成分具有进一步开发成药物的潜力,为后续进一步研究开发治疗NAFLD的创新药物提供一定的理论基础。     

钒酰腙配合物的合成、结构及生物活性

以酰腙为配体钒的单核、双核配合物因其结构丰富、生物活性多样而引起广泛关注。目前该领域新配合物的合成、表征和生物活性的研究甚为活跃。本文回顾了近年来钒酰腙配合物的研究状况,主要从以下三个方面进行综述：(1)钒酰腙配合物的合成方法;(2)此类配合物的配位模式;(3)一些单、双核钒酰腙配合物抗变形虫,抗肿瘤,类胰岛素,抑制Na⁺, K⁺-ATP酶,与DNA作用的生物活性。文中着重阐述了钒酰腙化合物的结构和生物活性之间的关系。此外,还提出了钒酰腙配合物研究领域的不足之处并对其今后发展方向进行了展望。     

从钒化合物生物效应的多样性看其作用机制*

本文对近年来关于钒化合物不同生物效应机制的研究进展进行了总结,着重于其类胰岛素和抗癌效应的信号转导机制以及两者之间的相关性。同时,基于钒化合物对磷酸转移反应的干预以及对细胞氧化还原状态的调节,讨论了钒化合物多样化的生物效应是否具有一个共同作用机制的可能性,并提出了未来钒化合物研究方向和所面临的挑战。     

核苷及其类似物的三磷酸化方法研究进展

三磷酸核苷是一种具有三个磷酸基团的核苷酸,不仅在细胞的能量代谢中起着重要作用,也可用于心脑血管和神经系统等许多疾病的治疗和辅助治疗,随着分子生物学的发展,三磷酸核苷在许多生物检测技术中也应用广泛。新冠疫情爆发以来,抗病毒核苷类药物成为研究的热点,这类药物大多在体外不具有活性,而是在细胞内代谢为三磷酸形式发挥作用,在对这类化合物的抗病毒机理研究中,研究其抗病毒活性、抗病毒机制等都需要将核苷类药物进行三磷酸化,因此开发一种高效的核苷三磷酸化方法是十分必要的。本文根据三磷酸核苷的合成历史进程,综述了迄今为止三磷酸核苷的化学合成方案。旨在为核苷及其类似物的三磷酸化以及相关药物的研发提供参考。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.