戊二酰亚胺类抗生素的研究进展*

戊二酰亚胺娄抗生素从链霉菌发酵液提取分离得到,具有抗真菌、抗细菌、抗原虫、抗病毒、抗肿瘤及免疫抑制等多种生物活性。本类抗生素包括具有经过多年发展的环己酰亚胺、S-632类以及斩近发现的具有明显抑制肿瘤细胞迁移的大环内酯结构的migrastatin家族等。现对戊二酰亚胺类抗生素及其类似物的结构、活性和构效关系进行综述,并简单介绍了几个非微生物来源及化学合成的酰亚胺类物质。     

戊二酰亚胺类抗生素S-632A对D-半乳糖老化小鼠海马神经元Aβ及其相关蛋白表达的影响

目的:观察戊二酰亚胺类抗生素S-632A对D-半乳糖老化小鼠模型(DGAM)海马神经元β-淀粉样肽(β-amyloid,Aβ)及其相关蛋白表达的影响.方法:采用免疫组织化学染色和免疫印记方法,检测DGAM海马神经元Aβ、β-分泌酶(Beta-site APP cleaving enzyme,BACE)、内质网Aβ结合蛋白(Endoplasmicreticulum amyloid β peptide binding protein,ERAB)和早老蛋白1(Presenilin-1,PS-1)的表达水平,并观察应用戊二酰亚胺类抗生素S-632A对DGAM海马神经元的保护作用.结果:对照组小鼠海马神经元Aβ及其相关蛋白BACE,ERAB和PS-1表达量少,而DGAM小鼠海马神经元Aβ及其相关蛋白表达水平明显增加,与对照组比较差异具有高度显著性(P<0.01),S-632A组上述各种蛋白的表达结果与对照组接近.结论:DGAM小鼠海马神经元存在着Aβ及其相关蛋白BACE,ERAB和PS-1表达的上调,S-632A可明显改善模型动物中上述蛋白的异常表达,对小鼠神经元具有营养和保护作用.     

薄层层析-紫外分光光度法在戊二酰亚胺类抗生素S632-A产品控制中的应用

目的:测定戊二酰亚胺类抗生素S632-A含量.方法:采用薄层层析法,对S632链霉菌发酵液成分进行分离,紫外分光光度法间接测定S632-A的含量,检测波长为233nm.结果:线性范围为5.7～34.2μg·mL-1(r=0.999 6),平均回收率为103.7%,精密度试验RSD为1.80%(n=5).结论:此方法较微生物测定法准确、简便、灵敏度高,适用于科研和生产过程中抗生素S632-A的产品控制.     

HPLC法测定抗生素S632-A中9-甲基链霉戊二酰亚胺的含量

目的:建立测定抗生素S632-A中9-甲基链霉戊二酰亚胺(S632-A2)含量的HPLC方法.方法:采用Agilent TC-C18柱(150 mm×4.6 mm,5 μm),流动相为甲醇-水(45:55);流速:0.6 mL·min-1,检测波长233 nm,柱温为室温.结果:S632-A2进样量在0.88～8.76 μg范围内呈良好的线性关系(r=0.9995),回收率为99.97%,RSD为0.33%(n=9).结论:此方法准确,重复性好,可为评价抗生素S632-A提供可靠依据.     

一系列新的3-硝基-1,8-萘二酰亚胺的合成和作用方式

天然产物马兜铃酸(1),它的β-硝基萘部分为抗肿瘤作用所必需。而它的某些类似物,包括许多β-硝基衍生物,在细胞培养中细胞毒性比它更强。抗生素环己亚胺(2)是蛋白质合成抑制剂,也是细胞毒素类药物,它象CG-603(3)[1-(吗啉基甲基)-4-邻苯二酰亚胺基哌啶-2,6-二酮]一样,是通过内分泌机理而起作用的。这两个化合物都含有一个戊二酰亚胺环,在(3)中它联结于侧链。此外,作用于DNA的抗病毒药物乙氨芴酮(4),有两个侧链,每一侧链都有一个叔胺基。作者试图将1～4中已知为活性所必需的化学结构合并在一个分子中,结果合成了四个新的3-     

干扰素的命名与分类

IFN是interferon的缩写，它的汉语译叫作“干扰素”。干扰素(IFN)是由机体细胞分泌的一类具有抗病毒活性等多种生物学功能的蛋白质。IFN在1957年被发现时是以抗病毒活性为其唯一活性的物质。随后研究发现，INF除具有抗病毒繁殖作用外，还具有抑制细胞分裂、免疫调节、抗肿瘤等一系列其它生物学活性。因此，1980年国际干扰素命名委员会给IFN下了如下定义：IFN是一类在同种细胞上具有广谱抗病毒活性的蛋白质，其活性的发挥又受细胞基因组的调节和控制，涉及RNA和蛋白合成。     

二氢杨梅素抗菌、抗病毒作用的研究进展

二氢杨梅素是葡萄科蛇葡萄属植物中广泛存在的二氢黄酮醇类化合物,具有抗炎、抗肿瘤、抗氧化、降血糖、调血脂、保肝等多种活性。近年来,二氢杨梅素在抗菌、抗病毒方面的生物学活性逐渐成为人们关注的热点。针对近些年来国内外有关二氢杨梅素在抗菌、抗病毒方面的研究进行综述,旨在为其在抗感染方面进一步的开发和临床应用提供思路。     

萘酰亚胺类化合物作为抗肿瘤药物的研发现状*

萘酰亚胺是一类具有良好抗肿瘤活性的化合物，主要分为单萘酰亚胺和双萘酰亚胺，处于临床研究阶段的分别有氨萘非特（amonafide）、米托萘胺（mitonafide）和依利萘法德（elinafide）、双萘法德（bisnafide）。具有抗肿瘤活性的萘酰亚胺类化合物大多是DNA嵌入剂，并且靶向拓扑异构酶Ⅱ。现以几个主要代表药物为例，介绍了萘酰亚胺类化合物的抗肿瘤活性、作用机制以及临床研究进展。     

植物多糖抗肿瘤与降血糖作用研究进展

植物多糖是一类生物大分子,具有抗肿瘤、降血糖、降血脂、抗氧化、抑菌和抗病毒等多种生物学活性。目前对植物多糖的研究越来越深入,尤其在抗肿瘤、降血糖方面的研究发展较快。故就近年来对植物多糖抗肿瘤与降血糖生物作用的研究进展进行综述,以期为探索植物多糖类新药物资源的开发应用提供参考。     

紫草素及其衍生物的药理作用研究进展

［摘要］紫草素及其衍生物提取自传统中药紫草。实验研究显示,紫草素及其衍生物具有抗炎、抗氧化、抗病毒、抗肿瘤等多种药理活性,对多种肿瘤细胞都有确切的抑制生长及促凋亡的作用。对心血管系统有保护作用 。在紫草素及其衍生物的众多药理活性中,其抗炎及抗肿瘤活性表现突出,是目前研究的热点和重点,有望成为治疗这类重大疾病的新药。     

Antiviral and antitumor structure-activity relationship studies on tetracyclic eudistomines.

The in vitro antiviral and antitumor activities of (-)-debromoeudistomin K (1a) and 10 structural analogues (1b-1j and 11) were evaluated. The synthesis was accomplished with an intramolecular Pictet-Spengler condensation reaction as the key step. This examination revealed some structural and stereochemical features that are important for both the antiviral and antitumor activities. The most striking points for activity are the necessity to have the correct natural stereochemistry at both C(1) and C(13b) and the presence of the C(1)-NH2 substituent. As was revealed before with naturally isolated eudistomins a substituent in the indole ring greatly influences the biological activity. The 5-OMe derivative 1h shows high potency in both antiviral and antitumor models.     

Novel linked antiviral and antitumor agents related to netropsin and distamycin: synthesis and biological evaluation

A group of oligopeptides have been synthesized which are structurally related to the natural antiviral antitumor antibiotics netropsin and distamycin bearing two such moieties linked by polymethylene bridges. Cytostatic activity against both human and murine tumor cell lines and their in vitro activity against a range of viruses are reported. Enhanced antiviral activity was obtained against vaccinia virus. As a result of the introduction of the polymethylene linkers [( CH2)n, with n = 1, 2, and 6-8], both the antitumor and antivaccinia virus activity was markedly enhanced, relative to that of the parent compounds netropsin and distamycin. The biological activity of these agents is discussed both in terms of their structural differences and in relation to their minor groove binding to duplex DNA.     

金丝桃属植物中的金丝桃素:化学、植物来源和生物活性(英文)

金丝桃素是金丝桃属植物中一种重要的次生代谢产物,1830年首次被正式报道,它是一种天然光敏型的二蒽酮类化合物。金丝桃素具有抗病毒,抗抑郁、抗肿瘤、抗菌、抗氧化等广泛的生物和药理活性,并用于光动力治疗。在过去的几十年中越来越多的证据表明金丝桃素具有很大的药用潜力和临床价值。本篇综述了金丝桃素的化学、植物来源和生物活性。     

氰基环氧化物分子内的环合反应

报道了氰基环氧化物分子内的环合反应及相关环戊烷衍生物的制备，这些化合物可以被用于具有抗肿瘤活性的前列腺素Ｊ２（ＰＧＪ２）和具有抗真菌，抗病毒及其他许多生物活性的（＋）－布雷菲德菌素Ａ（ＢＦＡ）的合成。     

2,4-Disubstituted thiazoles as multitargated bioactive molecules

Thiazoles are important heterocyclics exhibiting boundaryless biological activities, such as antibacterial, antifungal, anti-inflammatory, antitumor, antitubercular, antidiabetic, antiviral, and antioxidant. Substituents on a particular position of the thiazole ring affect the biological outcomes to a great extent. Therefore, researchers have synthesized compounds containing the thiazole ring with variable substituents as target structures, and evaluated their biological activities. The present review describes the biological importance of recently developed 2,4-disubstituted thiazole derivatives. Moreover, we have thrown light on various targets of 2,4-disubstituted thiazoles through which they induce biological effects, which will be helpful to those who are working on the design and structure–activity relationship of bioactive molecules.     

Phenylpropanoid sucrose esters: plant-derived natural products as potential leads for new therapeutics

Natural products are regarded as vital key source of lead compounds for drug discovery due to their structural diversity and broad array of biological activities. Phenylpropanoid sucrose esters are naturally occurring compounds isolated from various plants and are structurally characterized by a sucrose core connected to one or more Ph-CH=CH-CO- moieties through an ester linkage. These compounds were extensively used in folk medicine and are found to possess many biological activities such as antitumor, antibacterial, antioxidant, antiviral, anti-inflammatory, neuro-protective and glycosidase inhibitory activities. This extensive review, which is the first of its kind on phenylpropanoid sucrose esters, aims to provide an up-to-date account of naturally occurring known phenylpropanoid sucrose esters with special focus on their sources, structures, biological and pharmacological activities.     

茚满霉素类天然产物的研究进展

茚满霉素类天然产物是一类具有反式四氢茚满环(indan)结构的微生物次级代谢产物,该类化合物普遍具有良好的抗菌、杀虫以及抗肿瘤等生物活性,因而引起了药物化学家和生物学家的广泛兴趣。对1979年至今有关茚满霉素类化合物的天然发现、生物活性、化学合成以及生物合成等方面的研究进展进行综述,为该类抗生素的基础和应用研究提供科学参考。     

Perspectives on the development of novel potentially active quinolones against tuberculosis and cancer

Quinolones and its derivatives comprise an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, antitumor, antiviral, anti-ischemic, antiparasitic and anxiolytic. Persistent efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side-effects. The present review aims to highlight some recent discoveries on the development of novel quinolone-based compounds with potential antitubercular and anticancer activity.     

Synthesis of certain pyrimido[2,1-b]benzothiazole and benzothiazolo[2,3-b]quinazoline derivatives for in vitro antitumor and antiviral activities

Some new pyrimido[2,1-b]benzothiazole and benzothiazolo[2,3-b]quinazoline derivatives have been synthesized and tested for their antitumor and antiviral activities. Among therm, compounds 5c and 8d exhibited a broad spectrum antitumor activity with full panel (MG-MID) median growth inhibition (GI50) of 11.0 and 11.9 mumol/l, respectively. On the other hand, compounds 5c and 5d showed potential activity against Herpes simplex type-1(HSV-1) with 61 and 50% reduction in the viral plaques, respectively. The detailed synthesis, spectroscopic and biological data are reported.