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Synthesis of 2-(4-Hydroxyphenyl)benzofurans and Their Application to $\beta$-Amyloid Aggregation Inhibitor

  • Choi, Hong-Dae;Seo, Pil-Ja;Son, Byeng-Wha;Kang, Byoung-Won
    • Archives of Pharmacal Research
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    • v.27 no.1
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    • pp.19-24
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    • 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.

Different Functional and Structural Characteristics between ApoA-I and ApoA-4 in Lipid-Free and Reconstituted HDL State: ApoA-4 Showed Less Anti-Atherogenic Activity

  • Yoo, Jeong-Ah;Lee, Eun-Young;Park, Ji Yoon;Lee, Seung-Taek;Ham, Sihyun;Cho, Kyung-Hyun
    • Molecules and Cells
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    • v.38 no.6
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    • pp.573-579
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    • 2015
  • Apolipoprotein A-I and A-IV are protein constituents of high-density lipoproteins although their functional difference in lipoprotein metabolism is still unclear. To compare anti-atherogenic properties between apoA-I and apoA-4, we characterized both proteins in lipid-free and lipidbound state. In lipid-free state, apoA4 showed two distinct bands, around 78 and $67{\AA}$ on native gel electrophoresis, while apoA-I showed scattered band pattern less than $71{\AA}$. In reconstituted HDL (rHDL) state, apoA-4 showed three major bands around $101{\AA}$ and $113{\AA}$, while apoA-I-rHDL showed almost single band around $98{\AA}$ size. Lipid-free apoA-I showed 2.9-fold higher phospholipid binding ability than apoA-4. In lipid-free state, $BS_3$-crosslinking revealed that apoA-4 showed less multimerization tendency upto dimer, while apoA-I showed pentamerization. In rHDL state (95:1), apoA-4 was existed as dimer as like as apoA-I. With higher phospholipid content (255:1), five apoA-I and three apoA-4 were required to the bigger rHDL formation. Regardless of particle size, apoA-I-rHDL showed superior LCAT activation ability than apoA-4-rHDL. Uptake of acetylated LDL was inhibited by apoA-I in both lipid-free and lipid-bound state, while apoA-4 inhibited it only lipid-free state. ApoA-4 showed less anti-atherogenic activity with more sensitivity to glycation. In conclusion, apoA-4 showed inferior physiological functions in lipid-bound state, compared with those of apoA-I, to induce more pro-atherosclerotic properties.

The $^4A_2(^4F)\rightarrow^4T_1(^4F)$ Transitions of a $Co^{2+}$ Ion in Inse Single Crystals (Inse 달결정에서 $Co^{2+}$ 이온의 $^4A_2(^4F)\rightarrow^4T_1(^4F)$ 전이특성)

  • 박병서
    • Journal of the Korean Vacuum Society
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    • v.4 no.2
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    • pp.119-123
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    • 1995
  • Bridgman 방법으로 성장한 InSe: Co 단결정의 근적외 영역에서의 광흡수 특성을 상온에서 조사하였다. 1350, 1530, 1710nm 파장영역에서 Td 대칭을 갖는 Co2+ 이온의 4A2(4F)$\longrightarrow$4T1(4F)전이에 대응되는 3개의 흡수 peak를 관측하였다. 이 미세구조는 스핀-궤도 결합효과에 의하여 분리된 Co2+ 이온의 4T1(4F) 준위의 $\Gamma$6, $\Gamma$8, $\Gamma$7+$\Gamma$8 준위와 바닥상태 4A2(4F)의 $\Gamma$8 준위 사이의 전자전이에 기인하며, 결정장이론에 의하여 잘 설명되었다.

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Replicated Association between SLC4A4 Gene and Blood Pressure Traits in the Korean Population

  • Jin, Hyun-Seok;Eom, Yong-Bin
    • Biomedical Science Letters
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    • v.18 no.4
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    • pp.377-383
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    • 2012
  • Recent genome-wide association studies (GWAS) have identified a number of common variants associated with blood pressure homeostasis and hypertension in population. In the previous study, single nucleotide polymorphisms (SNPs) in the SLC4A4 gene have been reported to be associated with hypertension in Han Chinese population. We aimed to confirm whether the genetic variation of SLC4A4 gene influence the susceptibility to blood pressure and hypertension in Korean population. We genotyped variants in or near SLC4A4 in a population-based cohort including 7,551 unrelated Korean from Ansan and Ansung. Here, we performed association analysis to elucidate the possible relations of genetic polymorphisms in SLC4A4 gene with blood pressure traits. By examining genotype data of a total of 7,551 subjects in the Korean Association REsource (KARE) study, we discovered the SLC4A4 gene polymorphisms are associated with blood pressure and hypertension. The common and highest significant polymorphism was rs6846301 (${\beta}$=0.839, additive P=0.032) with systolic blood pressure (SBP), rs6846301 (${\beta}$=0.588, additive P=0.027) with diastolic blood pressure (DBP), and rs6846301 (OR=1.23, CI: 1.09~1.40, additive $P=1.2{\times}10^{-3}$) with hypertension. Furthermore, the SNP rs6846301 was consistently associated with both blood pressure and hypertension. Consequently, we found statistically significant SNPs in SLC4A4 gene that are associated with both blood pressure and hypertension traits. In addition, these results suggest that the individuals with the minor alleles of the SNP in the SLC4A4 gene may be more susceptible to the development of hypertension in the Korean population.

Intragenic DNA Methylation Concomitant with Repression of ATP4B and ATP4A Gene Expression in Gastric Cancer is a Potential Serum Biomarker

  • Raja, Uthandaraman Mahalinga;Gopal, Gopisetty;Rajkumar, Thangarajan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5563-5568
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    • 2012
  • Based on our previous report on gastric cancer which documented ATP4A and ATP4B mRNA down-regulation in gastric tumors relative to normal gastric tissues, we hypothesized that epigenetic mechanisms could be responsible. ATP4A and ATP4B mRNA expression in gastric cancer cell lines AGS, SNU638 and NUGC-3 was examined using reverse transcriptase PCR (RT-PCR). AGS cells were treated with TSA or 5'-AzaDC and methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis were performed. MSP analysis was on DNA from paraffin embedded tissues sections and plasma. Expression analysis revealed downregulation of ATP4A and ATP4B genes in gastric cancer cell lines relative to normal gastric tissue, while treatment with 5'-AzaDC re-activated expression of both. Search for CpG islands in their putative promoter regions did not indicate CpG islands (CGI) but only further downstream in the bodies of the genes. Methylation specific PCR (MSP) in the exon1 of the ATP4B gene and exon7 in ATP4A indicated methylation in all the gastric cancer cell lines tested. MSP analysis in tumor tissue samples revealed methylation in the majority of tumor samples, 15/19, for ATP4B and 8/8 for ATP4A. There was concordance between ATP4B and ATP4A down-regulation and methylation status in the tumour samples tested. ATP4B methylation was detectable in cell free DNA from gastric cancer patient's plasma samples. Thus ATP4A and ATP4B down-regulation involves DNA methylation and methylated ATP4B DNA in plasma is a potential biomarker for gastric cancer.

Synthesis of New 2,4-Disubstituted Thiazoles and 2-(Allylidenehydrazono)-thiazolo[5,4-b]quinoxaline Derivatives (새로운 2,4-이치환된 티아졸들과 2-(Allylidenehydrazono)-thiazolo[5,4-b]quinoxaline 유도체들의 합성)

  • Kim, Jong-Geun;Bae, Sun Kun
    • Applied Chemistry for Engineering
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    • v.20 no.2
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    • pp.134-139
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    • 2009
  • A series of allylidenethiosemicarbazone compounds (2a~2e) were obtained in 45~85% by condensing (E)-3-(aryl)acrylaldehyde (1a~1e) with thiosemicarbazide. Theses compounds on treatment of 2,4'-dibromoacetophenone and 2,3-dichloroquinoxaline yielded 2,4-disubstituted thiazoles (3a~3e) and 2-[(E)-3-(aryl)allylidenehydrazono]thiazolo[5,4-b]quinoxaline (4a~4e) in good yield respectively. The structures of all the newly synthesized compounds were identified by IR and $^1H-NMR$ spectral data.

Ulam Stability Generalizations of 4th- Order Ternary Derivations Associated to a Jmrassias Quartic Functional Equation on Fréchet Algebras

  • Ebadian, Ali
    • Kyungpook Mathematical Journal
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    • v.53 no.2
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    • pp.233-245
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    • 2013
  • Let $\mathcal{A}$ be a Banach ternary algebra over a scalar field R or C and $\mathcal{X}$ be a ternary Banach $\mathcal{A}$-module. A quartic mapping $D\;:\;(\mathcal{A},[\;]_{\mathcal{A}}){\rightarrow}(\mathcal{X},[\;]_{\mathcal{X}})$ is called a $4^{th}$- order ternary derivation if $D([x,y,z])=[D(x),y^4,z^4]+[x^4,D(y),z^4]+[x^4,y^4,D(z)]$ for all $x,y,z{\in}\mathcal{A}$. In this paper, we prove Ulam stability generalizations of $4^{th}$- order ternary derivations associated to the following JMRassias quartic functional equation on fr$\acute{e}$che algebras: $$f(kx+y)+f(kx-y)=k^2[f(x+y)+f(x-y)]+2k^2(k^2-1)f(x)-2(k^2-1)f(y)$$.

Two-dimensional Cu Coordination Polymer: [$Cu_2Cl_2$(4,4'-dipyen)] (2차원 구리 배위 고분자: [$Cu_2Cl_2$(4,4'-dipyen)])

  • Huh, Hyun-Sue;Lee, Soon-W.
    • Korean Journal of Crystallography
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    • v.18 no.1_2
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    • pp.16-20
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    • 2007
  • Under hydrothermal conditions, a 2-dimensional copper(I) coordination polymer [$Cu_2Cl_2$(4,4'-dipyen)] (1) was prepared from [$Cu(OAc)_2]{\cdot}H_2O$, 4,4'-dipyen, and KCl. In polymer 1, copper atoms are linked by the 4,4'-dipyen ligands approximately along the b-axis and are also linked by the chloro ligands approximately along the a-axis to form a 2-D layer, a network of rectangles.

An Efficient Synthesis of New Pyrazolines and Isoxazolines Bearing Thiazolyl and Etheral Pharmacophores

  • Bhosle, Manisha R.;Mali, Jyotirling R.;Pratap, Umesh R.;Mane, Ramrao A.
    • Bulletin of the Korean Chemical Society
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    • v.33 no.6
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    • pp.2012-2016
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    • 2012
  • A convenient synthetic route has been developed to synthesize 5-(4-((2-phenylthiazol-4-yl) methoxy)phenyl)-3-(4-sustituted phenyl)pyrazolines (5a-f) and 5-(4-((2-phenylthiazol-4-yl)methoxy)phenyl)-3-(4-substituted phenyl)isoxazolines (6a-f) starting from 2-phenyl-4-chloromethylthiazole (1). The chloromethylthiazole (1) was first condensed with 4-hydroxy benzaldehyde (2) for obtaining 4-((2-phenylthiazol-4-yl)methoxy)benzaldehyde (3). Claisen-Smidth condensation of 4-((2-phenylthiazol-4-yl)methoxy)benzaldehyde (3) and acetophenones has been carried in alkaline alcohol and obtained 3-(4-((2-phenylthiazol-4-yl)methoxy)phenyl)-1-(4-substituted phenyl)prop-2-en-1-ones (4a-f). The cyclocondensation of 2-propen-1-ones has been first time carried separately with hydrazine hydrate and hydroxylamine hydrochloride in aqueous micellar tetradecyltrimethylammonium bromide (TTAB) medium for getting the titled heterocycles with good to excellent yields.

Lactate Dehydrogenase and Monocarboxylate Transporters 1, 2, and 4 in Tissues of Micropterus salmoides (큰입우럭(Micropterus salmoides) 조직의 젖산탈수소효소 및 Monocarboxylate 수송체(MCT) 1, 2, 4)

  • Yum, Jung-Joo;Yeon, Jun-Hee
    • Journal of Life Science
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    • v.22 no.1
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    • pp.98-109
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    • 2012
  • The properties of lactate dehydrogenase (EC 1.1.1.27, LDH) and expression of monocarboxylate transporters (MCTs) 1, 2, and 4 were studied in tissues from Micropterus salmoides. Native-PAGE revealed that the LDH $A_4$ isozyme was predominantly located in skeletal muscle. The LDH $A_4$, $A_2B_2$, and $B_4$ isozymes were detected in heart, liver, eye, and brain tissues, while eye-specific $C_4$ isozyme was detected in eye tissue. In September, strong LDH $B_4$ isozyme activity was detected in heart tissue. High $A_4$ isozyme activity was noted in all other tissues except heart tissue. However, in November, strong $A_4$ isozyme activity was detected in heart tissue. The LDH/CS (Citrate synthase, EC 4.1.3.7) ratio in skeletal muscle and heart tissues indicated that anaerobic metabolism was high in those tissues. Native-PAGE after immunoprecipitation showed that eye-specific $C_4$ isozyme was more similar to the $A_4$ than the $B_4$ isozyme. The LDH $A_4$ isozyme was purified by affinity chromatography. The molecular weight of subunit A was 37,200. The LDH activity in tissues was consistently 11.05~28.32% due to inhibition by 10 mM pyruvate. The $K_m^{PYR}$ of LDH in eye tissue was very low. The optimum pH for LDH in tissues was pH 7.5~8.0. The LDH $A_4$ isozyme was detected in mitochondria of skeletal muscle, whereas the $B_4$ and $A_2B_2$ isozymes were detected in heart tissue mitochondria. Western blot analysis indicated that MCTs 1, 2, and 4 were located in the plasma membrane and mitochondria of skeletal muscle and heart tissues. The sizes of MCTs 1, 2, and 4 in skeletal muscle were 60, 54~38, and 63 kDa, while those in heart tissue were 57, 54~38, and 55.5 kDa, respectively. In conclusion, M. salmoides appears to use anaerobic metabolism predominantly when adapted to a hypoxic environment. In highly activated skeletal muscle and heart tissue, energy production is controlled by inward and outward flows of pyruvate and lactate through MCTs 1, 2, and 4 in the plasma membrane and mitochondria, with effective adjustment by LDH isozymes.