Analysis of Target Molecular and Preparation of Molecular Probes for Neurotrophic Low-Molecular Natural Products

神经营养性低分子天然产物的靶分子分析及分子探针的制备

基本信息

批准号：
16510172
负责人：
FUKUYAMA Yoshiyasu
金额：
$ 2.43万
依托单位：
Faculty of Pharmaceutical Sciences, Tokushima Bunri University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

This research project has been carried out aiming at search for new neurotrophic natural products and synthesis of the three known active compounds, honokiol, neovibsanin an talaumidin as well as for clarifying their neurotrophic mechanism. The following results have been obtained.(1)Screening natural products by using PC 12 cells has resulted in the discovery of five new active compounds, one of which is an ergosterol bearing an endoperoxide. This compound not only promotes significantly neurite outgrowth of PC 12, but also exhibits neurotrophic activity in the primary cultured rat cortical neurons. Another four neovibsanins have been isolated as neurotrophic substances from Viburnum sieboldii.(2)Honokiol has been synthesized by palladium-catalyzed Suzuki-Miyaura cross coupling as a key reaction. The structure units that are essential for neurotrophic activity have been identified. Several fluorescent derivatives attached to luminous groups (7-MCA or NBD) at the 3'-position were synth … More esized and then the distribution in neurons using them was investigated. Consequently, it was found that the fluorescent derivatives penetrated into the neuron and concentrated on the connecting region to the neurite. The competitive experiment between honokiol and the fluorescent derivatives suggest that the fluorescent derivatives of honokiol are likely to interact at the same site in the neurons as honokiol. These results indicate that honokiol can penetrate into the neuron and interacts at some specific proteins such as the enzyme.(3)The enantioselective synthesis of talaumidin has been accomplished by asymmetric Evans protocol, stereoselective hydroboration and highly controlled Firedel-Crafts arylation. This synthesis led to the conclusion of the absolute configuration of (2S,3S,4S,5S)-talaumidin, and allowed us to prepare its possible stereoisomers for structure-activity relationship.(4)Applying tandem Pd-catalyzed Heck and Trost reactions towards a diene system has developed the construction of the cyclohexane ring core fused with a tetrahydrofuran ring. This new methodology will be used for synthesis of neovibsanins. Less

该研究项目是为了寻找新的神经营养天然产物，并合成三种已知的活性化合物Honokiol，Neovibsanin a talamidin，以及澄清其神经营养机制。（1）使用PC 12细胞筛选天然产物已发现五种新的活性化合物，其中一种是一种伴有内过氧化物的麦角固醇。该化合物不仅促进了PC 12的明显神经落生物，而且在原代培养的大鼠皮质神经元中表现出神经营养活性。另外四个Neovibsanins已被分离为来自硫磺的神经营养物质。（2）Honokiol已通过钯催化的Suzuki-Miyaura Cross耦合合成，作为关键反应。已经确定了对神经营养活性必不可少的结构单位。在3'-position上附着在发光基团（7-mCA或NBD）上的几种荧光衍生物是合成器……更明显，然后研究了神经元中使用它们的分布。因此，发现荧光衍生物渗透到神经元中，并集中在连接区域与神经蛋白的连接区域上。 Honokio和荧光导数之间的竞争实验表明，Honokio的荧光衍生物很可能与Honokiol在神经元的同一位点相互作用。这些结果表明，Honokiol可以渗透到神经元中，并在某些特定的蛋白质（例如酶）上相互作用。（3）通过非对称Evans方案，立体选择性液压和高度控制的Firedel-Crafts芳基化，塔拉米蛋白的对映选择性合成已实现。该合成导致结论（2s，3s，4s，5s） - 塔拉米蛋白的绝对配置，并允许我们准备其可能的立体异构体以进行结构活性关系。（4）应用串联Pd-Pd-catalyzed Heck heck heck和Trost diene反应对二烯系统的构造开发了cyclohexane Reper core and core and core and core and core and core troff a torter forter forter forter forter fort forter fort forter fledy totry tatry tatry。这种新方法将用于合成新近蛋白酶。较少的

项目成果

期刊论文数量（60）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neurtrophic Effect of Magnolol in the Hippocampal CA1 Region of Senescence-Accelerated Mic (SAMP1).

厚朴酚对衰老加速麦克风 (SAMP1) 海马 CA1 区的神经营养作用。

DOI：
发表时间：
2005
期刊：
Biol. Pharm. Bull. 28・9
影响因子：
0
作者：
Ishihara;S.;Shiibashi;T.;Sato;Y.;Murata;K.;Nogami;S.;Uyama Tomohiko;宇山智彦;Uyama Tomohiko;Uyama Tomohiko;Uyama Tomohiko;Uyama Tomohiko;Yoshiyasu Fukuyama et al.;Yoshiyasu Fukuyama et al.
通讯作者：
Yoshiyasu Fukuyama et al.

Neurotrophic Effects of 1,4,Diaryl-2,3-dimethyltetrahydrofuran Lignans.

1,4,二芳基-2,3-二甲基四氢呋喃木脂素的神经营养作用。

DOI：
发表时间：
2005
期刊：
Biol.Pharm.Bull 27・2
影响因子：
0
作者：
Ishihara;S.;Shiibashi;T.;Sato;Y.;Murata;K.;Nogami;S.;Uyama Tomohiko;宇山智彦;Uyama Tomohiko;Uyama Tomohiko;Uyama Tomohiko;Uyama Tomohiko;Yoshiyasu Fukuyama et al.;Yoshiyasu Fukuyama et al.;Y.Fukuyama et al.;Yoshiyasu Fukuyama et al.
通讯作者：
Yoshiyasu Fukuyama et al.

トリシクロイリシノンを含む痴呆症治療薬

含有三环蓖麻酮的痴呆症治疗

DOI：
发表时间：
2005
期刊：
影响因子：
0
作者：
通讯作者：

Neurtrophic Effect of Magnolol in the Hippocampal CAI Region of Senescence-Accelerated Mic (SAMP1).

厚朴酚对衰老加速麦克风 (SAMP1) 海马 CAI 区域的神经营养作用。

DOI：
发表时间：
2005
期刊：
Biol.Pharm.Bull. 28, 9
影响因子：
0
作者：
千谷晃一;松井太衛;Y.Fukuyama et al.
通讯作者：
Y.Fukuyama et al.

Neurotrophic Effects of Talaumdin, a Neoliganan from Aristolochia arcuata, in Primary Cultured Rat

Talaumdin（一种来自马兜铃的新木脂素）对原代培养大鼠的神经营养作用

DOI：
发表时间：
2004
期刊：
Planta Medica 70・7
影响因子：
0
作者：
H.Noma;H.Tanaka;H.Noguchi;M.Shibuya;Y.Ebizuka;I.Abe*;Yoshiyasu Fukuyama et al.
通讯作者：
Yoshiyasu Fukuyama et al.