川芎嗪阿魏酸类化合物药理作用的研究进展

本文介绍了传统中药材川芎中的有效成分川芎嗪和阿魏酸的药理作用,并对近年来以川芎嗪和阿魏酸的结构为母核,按照拼合原理进行结构修饰的川芎嗪阿魏酸类衍生物进行了综述,为发现新的具有良好活性的化合物提供参考。     

查耳酮衍生物的结构修饰及生物活性研究进展

查耳酮类化合物广泛存在于天然植物中,具有抗癌、抗炎、抗氧化等多种药理活性。近年来,通过对大量具有查耳酮骨架的新型化合物的合成,查耳酮衍生物的生物活性也得到了深入研究。综述查耳酮衍生物的生物活性、结构修饰及构效关系的最新研究进展。     

大黄酸的结构修饰及其生物活性研究进展

大黄酸是大黄素型羟基蒽醌，主要存在于大黄等中药中。大黄酸具有抗癌、抗炎、抗菌、抗阿尔茨海默病等广泛的药理活性，但由于其水溶性差、生物利用度低等缺点，限制了其临床应用。为了克服这些缺点，研究者通过对其进行结构修饰研究，设计并合成了大量生物活性更为突出的大黄酸衍生物。本文综述了近年来大黄酸的结构修饰及其生物活性研究进展，为大黄酸类衍生物的进一步研究提供参考依据。     

小檗碱类抗微生物化合物研究进展

小檗碱类化合物是一类具有多种生物活性且大量应用于临床的季铵类异喹啉生物碱。近年来,小檗碱类药物的研究与开发受到广泛关注,且逐渐成为一个发展迅速、充满活力的领域。通过结构修饰所得的小檗碱类衍生物具有良好的抗细菌、抗真菌及抗病毒活性,可通过多种靶点对微生物发挥抑制作用。本文综述小檗碱类衍生物在抗细菌、抗真菌及抗病毒方面的研究与开发进展状况,为进一步研发小檗碱类抗微生物药物提供参考。     

异甜菊醇衍生物的生物活性及构效关系研究进展

异甜菊醇因具有贝叶烷四环二萜类的特征性骨架,并具有抗高血压、调血脂、降血糖、保护心脑细胞、抑菌、抗炎及抗肿瘤等广泛生物活性,且其制备原料甜菊苷廉价易得、安全低毒,故以其为先导物,通过化学合成和微生物转化,对其结构进行修饰与改造,发现具更高活性的异甜菊醇衍生物,已成为广受药学研究者关注的热点.综述近年来异甜菊醇衍生物的生物活性及构效关系研究进展.     

含有黄嘌呤衍生物的N-杂环卡宾金属配合物的生物活性研究进展

N-杂环卡宾(NHC)是一类多功能的配体,能够与过渡金属形成稳定的配位化合物,在催化、药学和材料科学等领域有着广泛的应用。黄嘌呤衍生物具有抗肿瘤转移和抗血管生成等生物活性,且结构易于修饰。将黄嘌呤衍生的NHC配体与过渡金属相结合有望得到具有全新生物活性的金属配合物。综述黄嘌呤衍生物的生物活性,以及黄嘌呤衍生的NHC金属配合物的结构特点和生物活性,并对黄嘌呤NHC金属配合物的研究进行了总结和展望,以期为进一步的研究提供参考。     

胡椒碱衍生物的化学合成及生物活性研究进展北大核心CSCD

胡椒碱具有抗肿瘤、抗炎和抑制微生物生长等广泛而优异的药理活性,目前以胡椒碱作为先导化合物进行结构修饰和改造的研究报道较多。本文将简要介绍胡椒碱衍生物的化学合成方法以及生物活性研究进展,阐明衍生物的化学结构与生物活性之间的关系,为胡椒碱类似物的进一步研究和开发提供参考与借鉴。     

大环内酯类抗生素糖基的结构修饰

大环内酯类抗生素是由链霉菌产生的一类弱碱性抗生素及通过其结构修饰得到的衍生物。为发现具有优良抗耐药活性和其他生物活性的化合物、解决当前日益泛滥的细菌耐药性,研究工作者对大环内脂酯类化合物进行了大量的结构修饰。本文在简要介绍大环内酯类抗生素的发展概况的基础上,重点对大环内酯类化合物结构中克拉定糖和去氧氨基糖的结构修饰及对生物活性的影响进行综述。     

阿魏酸衍生物的临床应用及开发前景

阿魏酸（ferulaic acid)是桂皮酸的衍生物之一，普遍存在于当归、川芎等常用植物药中。研究证明，其具有广泛的生物活性和药理作用。近年来，通过合成一系列阿魏酸衍生物。并对其药理活性进行观察和筛选，得到了一些药理作用强且毒副作用较低的化合物，其中有一部分已被应用于临床，并且取得了良好的治疗效果。     

喹诺酮类药物的结构修饰及“非经典”生物活性研究进展

喹诺酮类药物经过近50年的发展已成为一大类广泛用于临床的广谱、高效、低毒性的抗感染化疗药物。作为一类全合成药物,喹诺酮类结构中可供修饰的位点较多,其化学性质稳定,易于合成。结构修饰不仅是寻找抗菌活性更强的新喹诺酮的重要途径,也成为拓展其＂非经典＂生物活性的有效手段之一。10余年来,人们有针对性地设计合成了多个系列的喹诺酮类衍生物,评价了它们的＂非经典＂生物活性,并对其作用机制进行了初步探索,发现了一些苗头化合物。值得一提的是,喹诺酮类抗肿瘤候选药物SNS-595和HIV-1整合酶抑制剂埃替拉韦（elvitegravir,JTK-303,GS9137）目前均已进入临床试验阶段。本文系统综述了近年来喹诺酮类的结构修饰及其抗肿瘤、抗病毒、抗焦虑、抗缺血活性,以及作为潜在的Ⅱ型大麻素受体激动剂等方面的研究进展。     

川芎嗪的结构改造及修饰

综述了在川芎嗪结构改造及活性研究方面的进展。由于川芎嗪具有代谢快、半衰期短等不利于临床应用的药动学特性,人们根据前药原理,分别以川芎嗪及其体内活性代谢产物2-羟甲基-3,5,6-三甲基吡嗪为先导化合物,设计合成了川芎嗪酯类、醇类、醚类、胺类、烃类及氘代等衍生物,并通过筛选发现了一些具有较好心脑血管药理活性和良好药动学性质的化合物。     

Radical scavenger activity of phenylethanoid glycosides in FMLP stimulated human polymorphonuclear leukocytes: structure-activity relationships

Radical scavenger activities of 21 phenylethanoid glycosides, including 15 ester derivatives of caffeic, ferulic, vanillic and syringic acid as well as 6 deacyl derivatives were determined by quantifying their effects on the production of reactive oxygen species (ROS) in a luminol-enhanced chemiluminescence assay with formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated human polymorphonuclear neutrophils (PMNs). All phenylethanoids acylated with phenolic acids showed strong antioxidant activity whereas the deacyl derivatives were more than 30-fold less active. Therefore, the antioxidant activity is mainly related to the number of aromatic methoxy and hydroxy groups and the structure of the acyl moiety (C6-C1 or C6-C3). In contrast, modification of the sugar chain or replacement of hydroxy groups by methoxy groups in the acyl or the phenylethanoid moiety is of minor importance. The position of the acyl moiety is without significance. Free caffeic, ferulic, vanillic and syringic acid are less active compared to the phenylethanoid derivatives. This points to the importance of dissociation and lipophilicity of these acids in a cellular test system.     

青藤碱结构改造的研究进展

青藤碱是一种来源于防己科植物青风藤中的生物碱,在结构上属于异喹啉类,具有多种生物活性。在临床上主要用于治疗风湿性及类风湿性关节炎和心律失常等疾病。但由于其用药剂量大、对光/热不稳定、体内代谢快、易引起过敏反应,科研人员一直致力于对青藤碱进行结构修饰,以期开发出高效、低毒的青藤碱衍生物。对近年来青藤碱的结构修饰研究进展做一综述。     

五种酚类抗氧化剂活性差异的理论解释

AIM: To verify the effectiveness of structure-activity relationship (SAR) and theoretical calculation methods for antioxidants. METHODS: Preliminary elucidation on the differences of activities of 5 antioxidants was performed by SAR. Then semiempirical quantum chemistry method AM1 was employed to calculate the delta HOF value, the difference between the heat of formation of antioxidant and its free radical, which was used as a theoretical parameter to elucidate the differences of activities of the antioxidants thoroughly. RESULTS: delta HOF values of antioxidants were obtained as follows: ferulic acid, 150.58 kJ.mol-1; anion of ferulic acid, 122.64 kJ.mol-1; modified ferulic acid, 137.70 kJ.mol-1; anion of modified ferulic acid, 118.99 kJ.mol-1; salvianic acid, 134.17 kJ.mol-1; rutin, 137.83 kJ.mol-1, L-EGCG, 124.39 kJ.mol-1; paeonol, 176.79 kJ.mol-1. The differences of the antioxidant activities were elucidated, and how to further enhance the antioxidant activity was investigated as well. CONCLUSION: The SAR and calculation methods are rather effective to elucidate the differences of antioxidant activities, and present some new clues for structural modification of antioxidants to increase their activities.     

阿魏酸衍生物的合成及抗血小板聚集活性

以具有活血化瘀作用的中药有效成分阿魏酸为先导物,设计合成了6个阿魏酸衍生物,其结构经IR、1H NMR、13C NMR及MS确证。体内药效筛选结果显示,阿魏酸衍生物对二磷酸腺苷(ADP)诱导的血小板聚集具有较好的抑制活性,其抑制作用明显强于阳性对照药奥扎格雷钠。     

Hypothesis of potential active components in Angelica sinensis by using biomembrane extraction and high performance liquid chromatography

The screening and analysis of bioactive components in traditional Chinese medicines (TCMs) is very important not only for the quality control of crude drugs but also for elucidating the therapeutic principle. In this study, a method for screening potential active components from TCMs was developed by using biomembrane extraction and high performance liquid chromatography. Based on the methodology, aqueous extract of Angelica sinensis (WEAS) was used, and four compounds were detected by HPLC in the desorption eluate of red cell membrane extraction for WEAS. The compounds were identified as ferulic acid, ligustilide, senkyunolide H and senkyunolide I based on their UV, MS and NMR spectra. Actually, ferulic acid and ligustilide are considered as major active components in Angelica sinensis. Therefore, this method may be applied to predict the potential bioactivities of multiple compounds in TCMs simultaneously.     

Bioassay of ferulic acid derivatives as influenza neuraminidase inhibitors

Four series of ferulic acid derivatives were designed, synthesized, and evaluated for their neuraminidase (NA) inhibitory activities against influenza virus H1N1 in vitro. The pharmacological results showed that the majority of the target compounds exhibited moderate influenza NA inhibitory activity, which was also better than that of ferulic acid. The two most potent compounds were 1m and 4a with IC₅₀ values of 12.77 ± 0.47 and 12.96 ± 1.34 μg/ml, respectively. On the basis of the biological results, a preliminary structure–activity relationship (SAR) was derived and discussed. Besides, molecular docking was performed to study the possible interactions of compounds 1p , 2d , 3b , and 4a with the active site of NA. It was found that the 4-OH-3-OMe group and the amide group (CON) of ferulic acid amide derivatives were two key pharmacophores for NA inhibitory activity. It is meaningful to further modify the natural product ferulic acid to improve its influenza NA inhibitory activity.     

DPPH radical-scavenging effect of several phenylpropanoid compounds and their glycoside derivatives

Eugenol, isoeugenol, caffeic acid, ferulic acid, isoferulic acid, estragole, trans-anethole, and paeonol are components of a Chinese herbal medicine used as a painkiller and stomachic. We investigated the potential role of these compounds as antioxidants. We studied the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical-scavenging effect of these molecules, together with some glycoside derivatives, to ascertain their potential in reducing the levels of activated oxygen species in vivo. The DPPH radical-scavenging effects of eugenol, isoeugenol, and the glycoside derivatives of caffeic acid, ferulic acid, and isoferulic acid (SC(50)=8-28 microM) were similar to those of alpha-tocopherol, which was used as a positive control.     

Free and chemically bonded phenolic acids in barks of Viburnum opulus L. and Sambucus nigra L

Liquid column chromatography, planar chromatography (TLC) on modified and unmodified silica layers, reversed-phase high-pressure liquid chromatography (HPLC), as well as ESI-TOF MS and 1H-NMR have been used for separation, purification and identification of phenolic acids in the barks of Sambucus nigra and Viburnum opulus (Caprifoliaceae). By the use of these procedures three cinnamic acid derivatives: caffeic acid, p-coumaric, and ferulic acid, four benzoic acid derivatives: gallic acid, protocatechuic acid, syringic acid, 3,4,5-trimethoxybenzoic acid, two phenylacetic acid derivatives: 3,4-dihydroxyphenylacetic acid, homogentisic acid, and two depsides: chlorogenic acid and ellagic acid were detected and identified in the bark of Viburnum opulus. Caffeic acid, p-coumaric acid, ferulic acid, gallic acid, syringic acid, 3,4,5-trimethoxybenzoic acid and chlorogenic acid were also detected and identified in the bark of Sambucus nigra. Except for chlorogenic acid, this is the first time these phenolic acids have been isolated, detected, and identified in the bark of V. opulus and S. nigra.