紫杉醇的结构修饰及构效关系

本文总结了近年来对紫杉醇进行结构修饰所得到的近80种紫杉醇类似物的合成方法及其构效关系.     

灰树花活性多糖构效关系研究进展

灰树花是一种珍贵的食药用菌,具有降血糖、抗肿瘤、免疫调节和抗病毒等多种生物活性。灰树花多糖是其主要的活性成分,多糖的生物活性与多糖的结构密切相关。本文综述了从20世纪80年代起国内外已报道的灰树花活性多糖的结构表征。部分研究认为多糖的降血糖活性可能与β-1,6-葡聚糖主链化学结构相关,而灰树花多糖结构为β-1,6主链或β-1,3主链葡聚糖时具有较好的抗肿瘤活性。然而多糖结构异常复杂,精细结构的解析困难,导致目前灰树花多糖结构表征一般止步于单糖组成、分子量、糖苷键类型、分支结构和粗略分子链构象,但二维核磁(two dimensional nuclear magnetic resonance,2D-NMR)和高分辨质谱联用等技术的发展将有助于解开灰树花多糖构效关系,并为灰树花活性多糖的开发利用提供理论依据。     

应用量子化学方法研究茶多酚类抗氧化剂的构效关系

采用分子力学和量子化学从头计算方法,研究了不同结构茶多酚（Green tea polyphenol,GTP)抗氧化活性的构效关系。计算结果表明,茶多酚类的抗氧化活性与其释放活泼氢生成苯氧自由基的能力有关,添生大小与O－H间的Mulliken集居数、前线轨道能量、反应终态能量下降量及苯氧自由基稳定性有关。     

抗菌肽的特点及其构效关系

抗菌肽作为一类天然小分子多肽,因其独特的作用机制及广谱杀菌性,近年来备受人们的关注,在农、林、牧、渔业及药物制造等方面具有较大的使用价值。本文对其特点、构效关系做一综述。     

蜂毒溶血肽类似物定量构效关系计算分析

采用HyperChem7．0结构分析软件,对蜂毒溶血肽类似物的分予体积等结构参数进行了计算分析．分别利用多元线性回归、BP-神经网络计算法进行统计分析,获得两个相关性好的QsAR（quantitative structure-function relationship）模型．结果显示,蜂毒肽溶血活性与生成热、键合能、表面积、分予体积、极化能、醇水分配系数、水舍能相关．为降低溶血作用,指出在设计蜂毒肽结构时应尽量避免螺旋状结构．少用疏水性氨基酸．     

石蒜碱药理活性及构效关系研究进展

石蒜碱是药用石蒜科植物的有效成分之一,是重要的异喹啉类生物碱.石蒜碱拥有刚性的环系骨架、连续的手性中心、三级胺等独特的化学结构特征.同时其药理活性丰富多样,近年来,针对其抗癌、抗病毒、抗炎、抗寄生虫、抑制乙酰胆碱酯酶活性的研究越来越多,尤其在抗癌、抗病毒方面石蒜碱表现出较大潜力,特别是新型冠状病毒SARS-CoV-2研...     

食药用真菌多糖构效关系研究进展

真菌多糖具有抗病毒、抗凝血、抗肿瘤、免疫调节、降血脂、延缓衰老等多种生物活性,而多糖的功能与结构密切相关。多糖结构与功能关系的研究已经成为人们关注的一个热点。综述了食药用真菌多糖一级结构、高级结构及多糖的理化性质与其生物学活性之间的关系。     

单胺氧化酶抑制剂在临床方面的应用

单胺氧化酶(monoamine oxidase,MAO)是人体内天然存在的一种酶,催化单胺类物质氧化脱氨反应的酶。人体内含有两种单胺氧化酶:单胺氧化酶A和单胺氧化酶B。单胺氧化酶A主要分布在儿茶酚胺能神经元中;单胺氧化酶B主要分布在5-羟色胺能神经元、组胺能神经元和神经胶质细胞中,这两种亚型都均可以使单胺类神经递质失活。而单胺氧化酶抑制剂则能够通过抑制单胺氧化酶的对单胺类物质的氧化活性,从而达到减轻或者消除由各种原因引起的单胺类物质减少或单胺氧化酶活性过高导致的疾病。本文主要总结了近几年单胺氧化酶抑制剂在临床上用于治疗帕金森病、抑郁症和幽门螺旋杆菌方面的最新进展。     

单胺氧化酶抑制剂在临床方面的应用

单胺氧化酶（monoamine oxidase, MAO）是人体内天然存在的一种酶,催化单胺类物质氧化脱氨反应的酶。人体内含有两种单胺氧化酶：单胺氧化酶A 和单胺氧化酶B。单胺氧化酶A 主要分布在儿茶酚胺能神经元中;单胺氧化酶B 主要分布在5- 羟色胺能神经元、组胺能神经元和神经胶质细胞中,这两种亚型都均可以使单胺类神经递质失活。而单胺氧化酶抑制剂则能够通过抑制单胺氧化酶的对单胺类物质的氧化活性,从而达到减轻或者消除由各种原因引起的单胺类物质减少或单胺氧化酶活性过高导致的疾病。本文主要总结了近几年单胺氧化酶抑制剂在临床上用于治疗帕金森病、抑郁症和幽门螺旋杆菌方面的最新进展。     

黄酮类醛糖还原酶抑制剂的三维定量构效关系研究

目的：建立黄酮类化合物抑制剂活性的三维定量构效关系模型,为进一步进行黄酮类醛糖还原酶抑制剂（ARI）的活性与三维结构关系的研究提供重要依据。方法：采用比较分子力场分析法（CoMFA）和比较分子相似性指数分析法（CoMSIA）,系统研究了75个新型ARI的三维定量构效关系。结果：CoMFA和CoMSIA模型的交互验证相关系数q^2值分别为0.603和0．706、非交互验证相关系数r2值分别为0.956和0.900。结论：CoMFA和CoMSIA模型均具有较强的预测能力,CoMFA和CoMSIA模型的三维等值线图直观地解释了化合物的构效关系,阐明了化合物结构中各位置取代基对黄酮类醛糖还原酶抑制剂活性的影响,为进一步结构优化提供了重要理论依据。     

MDL 72145, an Enzyme-Activated Irreversible Inhibitor with Selectivity for Monoamine Oxidase Type B

Abstract: MDL 72145, ( E )-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine hydrochloride, was designed and synthesised as a potential enzyme-activated irreversible inhibitor of monoamine oxidase (MAO). In vitro , the compound displayed time-dependent pseudo-first-order irreversible inhibitory characteristics with high selectivity for the B form of rat brain mitochondrial MAO At 10°C the K_t and T₅₀ values for the B enzyme were 40 μ M and 1.7 min, respectively, while these same kinetic constants for the A enzyme were 131 μ M and 14.5 mm, respectively. Selective protection against inactivation of the two forms of MAO by MDL 72145 was obtained by preincu-bating the enzyme with suitable concentrations of the selective A and B substrates, 5-hydroxytryptamine and benzylamine.     

Models of Monoamine Oxidase A and B Active Sites Obtained by using 3D QSAR with CoMFA Analysis

Abstract

The monoamine oxidase catalyses the oxidative deamination of neuroactive amines. This enzyme exists in two forms A and B, which differ by substrates preference and inhibitors specificity. Investigation of the structures of these enzymes and design new selective inhibitors are of greatly interesting since MAO A inhibitors are used in therapeutic practice as antidepressants and MAO B inhibitors – in the treatment Parkinson's diseases. The three dimension structures of monoamine oxidases are still unknown. Therefore, one of the most perspective approach to define significant features of structure active site is method based on analysis of structure-activity relationship (3D QSAR) with comparison of molecular fields analysis (CoMFA) allowing to get the spatial distribution of important properties affecting the activity.

In present study we investigate the structures of active sites MAO A and B using 16 pyrazinocarbazole derivatives in variant conformation. Majority of pyrazinocarbazole derivatives have a rigit conformation, but three of those is sufficiently flexible. The latters can be in two conformation types: long molecules (substitution accommodate along axis of main structure) and short molecules (substitution accommodate at acute angle about of main structure). Several 3D QSAR and CoMFA models of MAO A and B active sites were design for data sets containing various types of flexible molecules conformation. All obtained models are statistical reliable and have sufficient predictive power for tested compound tetrindole. The best MAO A model that include two flexible molecules in long conformations was obtained, and the longest one of those in short conformation. In contrast, for MAO B model containing all flexible molecules in the short conformations is more preferred.

On the basis of obtained data the schematic models of MAO A and B active sites structures are proposed. According to these models MAO A active site have the narrow long cavity that accommodate long molecules, while MAO B active site is broader and shorter.     

Synthesis, antitumor activity and structure-activity relationships of a series of Ru(II) complexes

A series of octahedral Ru(II) polypyridyl complexes, [Ru(phen)(2)L](2+) (L=R-PIP and PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elementary analysis, (1)H NMR and ES-MS, as well as UV-visible spectra and emission spectra. The antitumor activities of these complexes and their corresponding ligands were investigated against mouse leukemia L1210 cells, human oral epidermoid carcinoma KB cells, human promyelocytic leukemia cells (HL-60) and Bel-7402 liver cancer cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. It was found that the complexes [Ru(phen)(2)L](2+) (L=R-PIP) exert rather potent activities against all of these cell lines, especially for the KB cells (IC(50)=4.7+/-1.3 microM). The binding affinities of these Ru(II) complexes to CT-DNA (calf thymus DNA), as well as the DNA-unwinding properties on supercoiled pBR322 DNA were also investigated. The results showed that these Ru(II) polypyridyl complexes not only had an excellent DNA-binding property but also possessed a highly effective DNA-photocleavage ability. The structure-activity relationships and antitumor mechanism were also carefully discussed.     

4-Mercaptoimidazoles derived from the naturally occurring antioxidant ovothiols 2. Computational and experimental approach of the radical scavenging mechanism

The radical-scavenging mechanism of fourteen 4-mercaptoimidazoles, derived from the natural family of ovothiols, was studied via a QSAR approach, cyclic voltammetry, ESR and NMR spectroscopy. A significant correlation was found between the DPPH scavenging abilities of test compounds and thermodynamic parameters like overall ease of disulphide formation. The production of a disulphide compound via thiyl radical formation is proposed. Upon DPPH scavenging, hydrogen abstraction from thiols yields transient short-lived thiyl radicals, which were characterised by ESR and rapidly dimerise to form a disulphide compound. Cyclic voltammetry showed that the best DPPH scavengers exhibit low oxidation potentials for their oxidation to disulphides.     

A quantitative structure-activity relationship study on matrix metalloproteinase inhibitors: Piperidine sulfonamide aryl hydroxamic acid analogs

A quantitative structure-activity relationship (QSAR) study has been made on a series of piperidine sulfonamide aryl hydroxamic acid analogs acting as matrix metalloproteinase (MMP) inhibitors. The inhibitory potencies of the compounds against two MMPs, MMP-2 and MMP-13, are found to be significantly correlated with the hydrophobic properties of the molecules, suggesting that in both enzymes the hydrophobic interaction is playing a dominant role.