• Bulletin of the Korean Chemical Society
• /
• 제31권4호
• /
• pp.1029-1030
• /
• 2010

• 한국자기공명학회논문지
• /
• 제26권1호
• /
• pp.17-20
• /
• 2022

High-pressure (HP) NMR is a versatile tool to investigate diverse features of proteins. This technique has been particularly powerful to elucidate structural dynamics that only populates sufficiently in a pressurized condition. Amyloidogenic proteins, which are prone to aggregate and form amyloid fibrils, often maintains highly dynamic states in its native or aggregation-prone states, and HP NMR contributed much to advance our understandings of the dynamic behaviors of amyloidogenic proteins and the molecular mechanisms of their aggregation. In this mini review, we therefore summarize recent HP NMR studies on amyloid-beta (Aβ), the representative amyloidogenic intrinsically disordered protein (IDP).

• 생약학회지
• /
• 제47권3호
• /
• pp.287-294
• /
• 2016

Acetylcholinesterase (AChE) activation and amyloid-${\beta}$ ($A{\beta}$) aggregation are major biological markers of Alzheimer's disease. In the present study, we evaluated the inhibitory effects of 50 kinds of herbal formulas on AChE activity and $A{\beta}$ aggregation. Among them, Hwanglyeonhaedok-tang, Cheonwangbosim-dan, Makmundong-tang, and Gamisoyo-san had a potent effects on the inhbition of AChE activity. Sosiho-tang, Samsoeum, Cheonsimyeunjaeum, and Bunsimgieum exerted to have the inhibitory activity on $A{\beta}$ aggregation. In addition, these 8 herbal formulas showed the 3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity, indicating their antioxidant activities.

• Bulletin of the Korean Chemical Society
• /
• 제30권6호
• /
• pp.1237-1238
• /
• 2009

• 약학회지
• /
• 제50권5호
• /
• pp.326-331
• /
• 2006

We designed and synthesized new benzylpiperidinyl ether derivatives as beta-amyloid aggregation inhibitors for the development of novel anti-Alzheimer's disease agents. As starting material, 4-hydroxypiperidine was used. For protection of the amine group in piperidine (2), di-tert-butyl dicarbonate was reacted with 4-hydroxypiperidine in the presence of triethylamine. For introduction of benzyl group, benzylbromide was treated with compound 2 in dioxane. After deprotection of Boc group on amine in compound 3, ester (5) was synthesized by addition of ethyl-4-chlorobutyrate. The alcohol 6 was synthesized by hydride reduction of 5 using $LiAlH_4$. To obtain final products (7-14), the alcohol 6 was condensed with each of substituted benzoic acids. To screen beta-amyloid aggregation inhibition of the products, thioflavinT assay was performed using $A{\beta}1-42\;at\;37^{\circ}C$ for 26 h incubation, in vitro. From the result of screening, compound 8, 9, 11 and 12 showed effective activity about $65{\sim}85\;{\mu}M\;as\;IC_{50}$ value. Among the prepared compounds, 4-[4-(benzyloxy)piperidino]butyl-4-chlorobenzoate (8) was the most effective inhibitor having $IC_{50}\;of\;65.4{\mu}M$.

• Journal of Microbiology and Biotechnology
• /
• 제13권5호
• /
• pp.809-814
• /
• 2003

${\beta}-amyloid$ ($A{\beta}$) peptides from the proteolytic processing of ${\beta}-amyloid$ precursor protein (${\beta}-APP$) aggregates in the brain to form senile plaques, and their aggregation plays a key role in pathogenesis of Alzheimer's disease (AD). To isolate an active compound that has an $A{\beta}$ aggregation-inhibitory activity, 2,000 microbial metabolite libraries were screened based on their ability to inhibit $A{\beta}$ aggregation by using both Congo red and thioflavin T assays. As a result, a water-soluble fraction of a soil microorganism, KK565, showed a potent $A{\beta}$ aggregation-inhibitory activity. The strain was identified as Streptomyces species, based on the cultural and morphological characteristics, the presence of diaminopimelic acid in the cell wall, and the sugar patterns for the whole-cell extract. In addition, the purification of active principle resulted in identifying a heat-unstable protein responsible for the $A{\beta}$ aggregation-inhibitory activity.

• 생약학회지
• /
• 제38권4호
• /
• pp.308-311
• /
• 2007

Inhibition of acetylcholinesterase and amyloid beta(1-42) peptide is good drug targets for Alzheimer's disease therapeutics. Among the twenty enthusiasm reducing herbals, the 70% methanol extracts (1 mg/ml) of Moutan Radicis Cortex and Forsythiae Fructus showed 91.5% and 85.3% about acethylcholinesterase inhibition, respectively. The extracts (1 mg/ml) of Coptidis Rhizoma and Paeoniae Radix Rubra showed more than 85% inhibition rate against amyloid beta (1-42) peptide aggregation. The neuroprotective effect of the extracts (1 mg/ml) of Moutan Radicis Cortex, Forsythiae Fructus and Paeoniae Radix Rubra showed 90.0%, 87.4% and 85.1% to compare with amyloid beta (1-42) peptide treated cells (IMR-32), respectively. Three herbs, Moutan Radicis Cortex, Forsythiae Fructus and Paeoniae Radix Rubra are promising candidates from natural products for development of Alzheimer's disease therapeutics.

• Archives of Pharmacal Research
• /
• 제26권12호
• /
• pp.985-989
• /
• 2003

An efficient synthesis of 5-chloro-3-[4-(3-diethylaminopropoxy)benzoyl]-2-(4-methoxyphenyl)benzofuran (8), a potent $\beta$-amyloid aggregation inhibitor, is described. 5-Chloro-2-(4-methoxyphenyl)benzofuran (3) was obtained by the one-pot synthesis of 4-chlorophenol with $\omega$(methylsulfinyl)-p-methoxyacetophenone (1) under Pummerer reaction conditions, and it was followed by the desulfurization of the resultant 5-chloro-3-methylthio-2-(4-methoxyphenyl)benzofuran (2e). Acylation of benzofuran 3 with 4-(3-bromopropoxy)benzoyl chloride (6) gave the ketone 7, which was converted into compound 8 by the treatment of diethylamine.

• Archives of Pharmacal Research
• /
• 제27권1호
• /
• pp.19-24
• /
• 2004

The facile synthesis of a series of 2-(4-hydroxyphenyl)benzofurans (4a-e) is described. The one-pot reaction of 4-substituted phenols with the chloride 1 in the presence of zinc chloride afforded 3-methylthio-2-(4-acetoxyphenyl)benzofurans (2a-e). The compounds 4a-e were obtained from the hydrolysis of 2a-e followed by the desulfurization of the resulting 3-methylthio-2-(4-hydroxyphenyl)benzofurans (3a-e). 5-Methyl-3-p-toluoyl-2 -[4-(3-diethylaminopropoxy)phenyl]benzofuran (7), a $\beta$-amyloid aggregation inhibitor, was synthesized by three steps starting from 4a.

• Archives of Pharmacal Research
• /
• 제28권11호
• /
• pp.1219-1223
• /
• 2005

6-[2-(Benzoxazol-2-ylmethylamino)ethoxy]-1-alkyl-1H-indole-2-carboxylic acids were designed and synthesized as $\beta$-amyloid (A$\beta$) fibril assembly inhibitors. Their inhibitory activity on A$\beta$, aggregation was evaluated by thioflavin T assay although their activities were insignificant.