芪参益气滴丸治疗心血管疾病的计算药理学研究

利用计算药理学方法研究了中药芪参益气滴丸中含1729个化合物在化学空间分布,结果表明大部分化合物具有较好的类药性质．利用分子对接方法研究了1729个与26个心血管疾病相关的公认靶标的相互作用及它们在靶空间的分布,阐明了芪参益气滴丸抗血管疾病的可能作用机理及活性分子．     

药物发现中常用化合物库特征描述与对比分析

随着计算技术的发展和分子模拟软件的日趋成熟, 虚拟筛选已经在药物发现过程中发挥着越来越重要的作用. 在虚拟筛选过程中, 所使用化合物库的质量对先导化合物发现的成功率起着至关重要的作用. 本文通过对已知药物库、天然产物库、中药原植物化学成分库、筛选常用商业化合物库以及研究者所在实验室建立的化合物库的分析比较, 从化合物库的分子多样性、化学空间和分子骨架等多个方面提取并对比每一种化合物库的特征, 发现了已知药物库与中药原植物化学成分库的特征相似性, 揭示了中药原植物化学成分库作为筛选库的类药性优势, 并且深化了对几种筛选用化合物库特征的认识和理解.     

系统药理学法研究“上火”与氧化应激之间的关系

运用中药系统药理学来分析黄连解毒汤,进而研究"上火"与氧化应激之间的关系.运用系统药理学中的靶点预测和网络药理学部分用来研究黄连解毒汤的抗氧化机制.具体来说,对黄连解毒汤的22个活性组分做靶点预测,发现有38个靶点与之相互作用,其中10个靶点与其抗氧化机制有关.且黄连解毒汤的抗氧化机制在组分水平、靶点水平、靶点对细胞因子水平上都有体现.从药理学角度,黄连解毒汤的抗氧化作用显著,与其在中药中强大的"清火"功能相对照后,就可以看出"上火"与氧化应激密切相关.将系统药理学应用于中药的方法,为"上火"的研究提供了一条新的思路.     

利用网络药理学方法研究热毒宁注射液抗流感病毒的分子作用机制

采用分子对接、网络分析预测热毒宁注射液抗流感病毒的分子作用机制, 并通过已建立的体外流感病毒神经氨酸酶筛选模型对网络预测结果验证. 结果表明, 热毒宁注射液所含化合物在化学空间上具有类药性质; 网络分析揭示出热毒宁注射液是通过与流感病毒吸附、脱壳、复制以及释放等环节的多个蛋白相互作用发挥抗流感病毒作用的; 对于预测的15 个活性分子而言, 实验结果初步证实, 对A型流感病毒, 木犀草素呈现较强的抑制作用, 槲皮素则呈现较弱的抑制作用, 这也初步证实了预测结果.     

中药作用靶点方法学研究进展

靶点(drug target)是药物作用的源头,是药物治疗疾病最直接、最重要、最初始的生物学基础.长期以来,中药由于其自身成分复杂的特点,关于作用靶点的揭示与阐明,以及分子药理机制等相关研究一直未能获得突破性进展,因此严重制约了中药的现代化和国际化进程.但是近年来,随着分子生物学、化学生物学以及生物物理学等前沿学科的发展,人们不断摸索和建立了一系列药物靶点的鉴定和识别方法,并尝试将这些方法应用于中药活性成分以及中药复方的作用靶点研究中,且取得了不少原创性成果,极大地推动了中医药的前进步伐.本文总结了近年来在中药靶点研究中出现的新方法与新策略,希望能够对从事中药现代化研究的人们提供全新思路,并拓展新的研究方向,最终促进中医药现代科学研究取得更大的突破.     

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。     

钒化合物的靶点蛋白及其生物效应

作为一种生物相关的金属元素,基于钒的金属化合物在糖尿病、癌症、阿尔茨海默症、神经炎症等疾病的治疗方面表现出独特的潜在应用价值。现阶段研究表明,钒发挥其生物活性主要源于钒酸根作为磷酸根类似物对细胞内磷酸转移反应的影响,及钒在细胞内经氧化还原转化产生的活性氧物质对相关信号通路的调节;而钒化合物与细胞内靶点蛋白的相互作用亦被认为是发挥其治疗作用的关键因素。本文就钒的化学性质、钒化合物与血清蛋白的结合、钒化合物对细胞内效应靶点蛋白及其作用通路的调控、细胞内金属药物靶点蛋白分析鉴定等几方面,对近年来取得的相关研究的进展进行综述,以系统性阐释钒化合物用于疾病治疗的生物活性机制,并对进一步揭示钒化合物作用机理的探索方向及其药用前景进行展望。     

抗AD活性天然化合物的结构与功能

阿尔茨海默症(Alzheimer's disease, AD)已成为影响人类健康的第四大杀手,给全球公共健康带来重大影响与挑战.近年来,新型治疗AD药物的研制成为生命与健康领域的重要课题,如何发现具有抗AD活性的苗头分子和先导结构是其中的关键科学问题与技术难点.植物来源的天然化合物具有多骨架、多活性、多靶点的成药性特征.本文综述了AD的发病机制和具有抗AD活性的天然化合物的化学结构与功能,为新型抗AD药物的研制提供参考.     

靶向分枝菌酸生物合成的抗结核化合物研究进展

结核病近年来已超过艾滋病成为当今世界范围内致死率高的感染性疾病之一.结核病耐药问题严峻,耐多药结核病治愈率低、治疗方案复杂且周期长.抗耐药结核领域存在重大研究机遇,亟需发现与发展针对新靶点的新化学实体.分枝菌酸的生物合成和转运途径富含抗结核药物的有效靶点,综述了靶向该途径的抑制剂,讨论了其作用机制、药代动力学性质等最新研究进展.     

聚集诱导发光体系:化合物种类、发光机制及其应用

聚集诱导发光(AIE)体系是近年来备受关注的一个研究领域,目前该领域已经积累了较为丰富的AIE化合物的分子设计理念和相应的对AIE机制的理解。AIE体系的研究为固态强发光材料特别是备受聚集发光猝灭难题困扰的有机电致发光材料提供了全新的分子设计思路。本文纵观该领域的研究进展,对AIE化合物种类、发光机制及其相关应用做出了较为详尽的综述报道。具有AIE性质的化合物主要包括多芳基取代的杂环化合物、多芳基乙烯类化合物、分子内电荷转移化合物、含有氢键的化合物、聚合物等。这些化合物的AIE发光机制也各有不同,包括分子内旋转受限、非辐射失活衰减受限、分子构象扭曲以避免形成激基缔合物以及利用特殊的分子堆积方式如J-聚集、交叉分子堆积、由分子间的C—H…π作用或特殊的氢键作用形成相应的发光聚集体等。基于其特殊的AIE性能,AIE化合物可广泛应用于化学传感、生物传感、生物标记、电致发光以及逻辑门器件等领域。     

Gold Complexes in Anticancer Therapy: From New Design Principles to Particle-Based Delivery Systems

The discovery of the medicinal properties of gold complexes has fuelled the design and synthesis of new anticancer metallodrugs, which have received special attention due to their unique modes of action. Current research in the development of gold compounds with therapeutic properties is predominantly focused on the molecular design of drug leads with superior pharmacological activities, e.g., by introducing targeting features. Moreover, intensive research aims at improving the physicochemical properties of gold compounds, such as chemical stability and solubility in the physiological environment. In this regard, the encapsulation of gold compounds in nanocarriers or their chemical grafting onto targeted delivery vectors could lead to new nanomedicines that eventually reach clinical applications. Herein, we provide an overview of the state-of-the-art progress of gold anticancer compounds, andmore importantly we thoroughly revise the development of nanoparticle-based delivery systems for gold chemotherapeutics.     

The genus Caesalpinia L. (Caesalpiniaceae): phytochemical and pharmacological characteristics

The genus Caesalpinia (Caesalpiniaceae) has more than 500 species, many of which have not yet been investigated for potential pharmacological activity. Several classes of chemical compounds, such as flavonoids, diterpenes, and steroids, have been isolated from various species of the genus Caesalpinia. It has been reported in the literature that these species exhibit a wide range of pharmacological properties, including antiulcer, anticancer, antidiabetic, anti-inflammatory, antimicrobial, and antirheumatic activities that have proven to be efficacious in ethnomedicinal practices. In this review we present chemical and pharmacological data from recent phytochemical studies on various plants of the genus Caesalpinia.     

Strecker reaction and α-amino nitriles: Recent advances in their chemistry,synthesis, and biological properties

α-Amino nitrile compounds have a profound impact on bio-chemical sciences, as they have been prepared from inexpensive starting materials and have become valuable intermediates in the chemical synthesis of vitally important heterocyclic and carbocyclic molecules, which serve as suitable models in pharmacological and biological research. The α-amino nitrile moiety has been found in the structure of different alkaloids, while the α-amidoacetonitrile group is an essential fragment of new anti-hyperglycemic drugs and promising pharmacological and agrochemical agents. Due to their synthetic, biological and practical importance, this review highlights the recent information about the preparation of α-amino nitriles through the Strecker-type and α-cyanation reactions, their chemical and biological properties, as well as their synthetic application, paying attention on the wonderful capacity for generating novel molecular diversity for pharmacological, biological and agrochemical researches, which ends with the total synthesis of complex alkaloids, preparation of new N-heterocycles and α-aminonitrile-containing drugs. Analyzing modern synthetic protocols for the Strecker-type reactions and cyanation reactions based on cross-dehydrogenative coupling (CDD) process, the advantages and disadvantages of new catalysts and green reaction conditions are also discussed. In addition, remarkable biological properties of α-amidoacetonitrile derivatives as potent and selective protease inhibitors as well as promising pesticidal agents were briefly reviewed. The bibliography includes 461 references.     

Liquid Chromatographic Analysis of Some N-Alkyl-3,4-methylenedioxyamphetamines

Abstract

The liquid chromatographic separation of a series of low molecular weight N-alkyl derivatives of 3,4-methylenedioxyamphetamine (MDA) is reported. The N-methyl-, N-ethyl- and N,N-dimethyl-derivatives of MDA have appeared as street drugs in recent years. These compounds are becoming significant forensic problems due to their unique pharmacological properties and relative ease of chemical synthesis. These amines were synthesized via reductive amination of the corresponding ketone with alkylamines. The UV absorption spectra for these compounds produced almost equally intense absorbance at 234 and 285 nm. The compounds were separated by reversed-phase (C₁₈) HPLC procedures using a mobile phase of aqueous methanol at low pH.     

Phytotherapy Perspectives for Treating Fungal Infections,Migraine, Sebhorreic Dermatitis and Hyperpigmentations with the Plants of the Centaureinae Subtribe (Asteraceae)

Sesquiterpene lactones, coumarins, phytoecdysones and phenolic compounds are characteristic of the species from the subtribe Centaureinae (Asteraceae). Many of the compounds isolated from plants of the Centaureinae subtribe have strong pharmacological properties. It may be suggested that these compounds’ chemical structure might be an indicator of these pharmacological properties. The aim of the study was to describe recent studies in the field of phytotherapy, focusing on compounds isolated from chosen plants of Centaureinae and the possibilities of using them to treat antifungal infections, inhibit serotonin and ease symptoms of seborrhea dermatitis and hyperpigmentation. The results of these biological studies have shown that in the future, extracts from the above-mentioned plant material may be used as active substances in new safe and effective drugs.     

A study of hydration effects on the conformational aspects of gaba mediators

The conformation of numerous chemical compounds is strongly influenced by solvents. Knowledge of their structure in solution is necessary, especially for a discussion of the biological and pharmacological activity of the molecules. The neurotransmitters and their agonists and antagonists are known to be flexible molecules that interact with quite distinct receptors. The conformational properties of several GABA (γ-aminobutyric acid) mediators have been studied by the MNDO technique. The optimized geometries of the molecules have been used to study the solvent effects on their conformational properties considering the supermolecule approach for their first hydration shell. A conjectural pharmacophoric pattern for several GABA inhibitors has already been suggested from the molecular electrostatic potentials (MEP ) of several molecules using a localized bond orbital technique. In the present work, MEP calculations have been carried out considering a solvent effect on the MNDO optimized geometries to investigate any deviation from the earlier results.     

Synthesis, Analgesic, and Antiparkinsonian Profiles of Some Pyridine, Pyrazoline, and Thiopyrimidine Derivatives

Summary. A series of substituted pyridine, pyrazoline, and thiopyrimidine derivatives were synthesized from 3-acetylpyridine, which was prepared from nicotinic acid as a naturally starting material. The pharmacological screening showed that many of these compounds have good analgesic and antiparkinsonian activities comparable to Voltarene^? and Benzatropine^? as reference drugs. The structure assignment of the new compounds is based on chemical and spectroscopic evidence. The detailed synthesis, spectroscopic data, and pharmacological properties for synthesized compounds are reported.     

Synthesis and antiinflammatory activity of some pyrimidines and thienopyrimidines using 1-(2-Benzo[d][1,3]dioxol-5-yl)vinyl)-4-mercapto-6-methylpyrimidine-5-yl)ethan-2-one as a starting material

In continuation to our search for new heterocyclic systems based antiinflammatories, the suggestion and synthesis of some pyrimidines, thienopyrimidines, and their derivatives, were herein realized. The pharmacological screening showed that many of these compounds have good antiinflammatory activity. The structure assignments of the new compounds are based on chemical and spectroscopic evidence. The detailed synthesis, spectroscopic data, and pharmacological properties are reported. Correspondence: Abd El-Galil Elsayed Amr, National Research Center, Organic Chemistry Department, Cairo, Dokki, Egypt.