• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1627-1637
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• 2012

The coupling reaction between 5-bromo-3-phenylbenzo[c]isoxazole and diphenylamine followed by further condensation with a mono-, di- or ter-acetyl aromatic compound in the presence of diphenyl phosphate at $145^{\circ}C$ gave a novel asymmetric diarylquinolines, oligoquinolines with diphenylamine endgroups, and a first generation quinoline dendrimer in 41-82% isolated yield. The electrochemical and photophysical properties of the oligoquinolines were characterized by cyclic voltammograms (CVs) and spectroscopy. All the quinolines emit bright sky blue light due to charge transfer from quinoline group to diphenly amine with very high quantum efficiency (> 90%). Organic light-emitting diodes (OLEDs) were fabricated using these quinolines as emitting materials. Among different device architectures explored, OLEDs with a structure of ITO/PEDOT (40 nm)/TAPC (15 nm)/D-A quinoline (40 nm)/TPBI (30 nm)/LiF (1 nm)/Al using TAPC as an electron blocking layer and TPBI as a hole blocking layer gave the best performance. A high external quantum efficiency in the range of 1.2-2.3% were achieved in all the quinolines with the best performance in BBQA(5). Our results indicate diarylamino-substituted oligoquinoline and dendrimer are promising materials for OLEDs applications.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.104-114
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• 2024

Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.874-878
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• 2006

Methyl gallate (MG) is a medicinal herbal product that is isolated from Paeonia lactiflora that inhibits cyclooxygenase-2 (COX-2) dependent phases of prostaglandin $D_2\;(PGD_2)$ generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with an $IC_{50}$ values of $17.0\;{\mu}M$. This compound also found inhibited the COX-2-dependent conversion of the exogenous arachidonic acid to $PGD_2$ in a dose-dependent manner with an $IC_{50}$ values of $190\;{\mu}M$, using a COX enzyme assay kit. However, at concentrations up to $80\;{\mu}M$, MG did not inhibit COX-2 protein expression in BMMC, indicating that MG inhibits COX-2 activity directly. Furthermore, MG consistently inhibited the production of leukotriene $C_4\;(LTC_4)$ in a dose dependent manner, with an $IC_{50}$ value of $5.3\;{\mu}M$. These results demonstrate that MG has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity, which might provide the basis for novel anti-inflammatory drugs.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.127-134
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• 2021

Neuroinflammation―a common pathological feature of neurodegenerative disorders such as Alzheimer's disease―is mediated by microglial activation. Thus, inhibiting microglial activation is vital for treating various neurological disorders. 7,3',4'-Trihydroxyisoflavone (THIF)―a secondary metabolite of the soybean compound daidzein―possesses antioxidant and anticancer properties. However, the effects of 7,3',4'-THIF on microglial activation have not been explored. In this study, antineuroinflammatory effects of 7,3',4'-THIF in lipopolysaccharide (LPS)-stimulated BV2 microglial cells were examined. 7,3',4'-THIF significantly suppressed the production of the proinflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) as well as of the proinflammatory cytokine interleukin-6 (IL-6) in LPS-stimulated BV2 microglial cells. Moreover, 7,3',4'-THIF markedly inhibited reactive oxygen species (ROS) generation. Western blotting revealed that 7,3',4'-THIF diminished LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), glycogen synthase kinase-3β (GSK-3β), and nuclear factor kappa B (NF-κB). Overall, 7,3',4'-THIF exerts antineuroinflammatory effects against LPS-induced microglial activation by suppressing mitogen-activated protein kinase (MAPK) and NF-κB signaling, ultimately reducing proinflammatory responses. Therefore, these antineuroinflammatory effects of 7,3',4'-THIF suggest its potential as a therapeutic agent for neurodegenerative disorders.

• Journal of Applied Biological Chemistry
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• v.65 no.1
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• pp.33-41
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• 2022

Esculetin (also known as 6, 7-dihydroxycoumarin) a type of coumarin, has been exhibited anti-inflammatory and anti-aging effects. Biorenovation is the microbe-mediated enhancement of biological efficacies and structurally diversified compounds relative to their substrate compounds. The production of different kinds of esculetin derivatives using Bacillus sp. JD3-7 and their effects on lipopolysaccharide (LPS)-triggered inflammatory response in RAW 26.7 cells were assessed. One of the biorenovation products, identified as esculetin 6-O-phosphate (ESP), at concentrations of 1.25, 2.5, and 5 μM inhibited the LPS-stimulated production of inflammation markers of nitric oxide synthase 2 and cyclooxygenase 2 as well as their respective enzymatic reaction products of nitric oxide and prostaglandin E2 in the order of increasing concentrations (1.25, 2.5, and 5 μM). Additionally, ESP treatment suppressed the LPS-stimulated secretion of pro-inflammatory cytokines of interleukin (IL)-1β, IL-6, and tumor necrosis factor- α. Furthermore, these anti-inflammatory effect of ESP was associated with the downregulation of mitogen-activated protein kinase signaling, that is, extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase signaling pathways. This study would therefore provide interesting insights into the biorenovation-assisted generation of a novel anti-inflammatory compound. ESP may be used to develop treatments for inflammatory disorders.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.360-367
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• 2022

Tropomyosin receptor kinase A (TrkA) protein is a receptor tyrosine kinase encoded by the NTRK1 gene. TrkA signaling mediates the proliferation, differentiation, and survival of neurons and other cells following stimulation by its ligand, the nerve growth factor. Chromosomal rearrangements of the NTRK1 gene result in the generation of TrkA fusion protein, which is known to cause deregulation of TrkA signaling. Targeting TrkA activity represents a promising strategy for the treatment of cancers that harbor the TrkA fusion protein. In this study, we evaluated the TrkA-inhibitory activity of the benzoxazole compound KRC-108. KRC-108 inhibited TrkA activity in an in vitro kinase assay, and suppressed the growth of KM12C colon cancer cells harboring an NTRK1 gene fusion. KRC-108 treatment induced cell cycle arrest, apoptotic cell death, and autophagy. KRC-108 suppressed the phosphorylation of downstream signaling molecules of TrkA, including Akt, phospholipase Cγ, and ERK1/2. Furthermore, KRC-108 exhibited antitumor activity in vivo in a KM12C cell xenograft model. These results indicate that KRC-108 may be a promising therapeutic agent for Trk fusion-positive cancers.

• Applied Biological Chemistry
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• v.40 no.4
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• pp.283-288
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• 1997

The antioxidant activities of Korean Red Ginseng Extract(RGE) and ${\alpha}-tocopherol$, as reference compound, were tested with HPLC and fluorometry which measure the MDA after reacting an aqueous 1% linoleic acid buffer solution, and LDL(1 mg protein/ml) buffer solution with $H_2O_2{\;}and{\;}FeCl_2$. The generation of conjugated-diene in LDL(0.25 mg protein/ml) was also measured by spectrometry. MDA determination showed the antioxidant effect on linoleic acid oxidation with oxidation inhibition ratio of 71.8% and 76.1%, respectively, by addition of 1000 ppm RGE and 100 ppm ${\alpha}-tocopherol$. LDL(1 mg protein/ml) oxidation was inhibited by 25.2% and 21.2%, respectively, by addition of 200 ppm REG and 100 ppm ${\alpha}-tocopherol$. The generation of conjugated diene in LDL(0.25 mg protein/ml) was also inhibited by 44.2%, by addition of 50 ppm RGE.

• Journal of the Korean Society of Food Culture
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• v.35 no.6
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• pp.597-604
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• 2020

This study examined the bioactive compound content and the antioxidant activities of bitter melon (Momordica charantia Linn.) leaves. The content of vitamin C, beta-carotene, and total carotenoids was 69.77, 45.68, and 65.08 mg/100 g, respectively. To investigate the antioxidant capacity, bitter melon leaves were extracted using various concentrations of ethanol (60, 80, or 100%). Highest content of total polyphenols (18.07 mg gallic acid equivalent/g) and flavonoids (4.53 mg cathechin equivalent/g) was found in the 100% ethanolic extract of the leaves (E100). Also, the E100 extract showed the highest levels of 2,2'azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and α-α-diphenyl-β-picrylhydrazyl (DPPH) free radical scavenging activities. Reducing power was also the highest (39.21 mg Trolox equivalent/g) in E100 extract. The E100 extract effectively inhibited lipid peroxidation by 91.45% compared to the control group. Also, the E100 extract showed a cytoprotective effect against oxidative stress in HepG2 cells and decreased the generation of intracellular reactive oxygen species. These results suggest that bitter melon leaves could be regarded as a potential source of natural antioxidants.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.62-62
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• 2003

It is now convincing that free radical generation is involved in the pathophy siological mechanisms of ischemic stroke, particularly in ischemia-reperfusion injury. The present study, therefore, examined neuroprotective effect of aloesin isolated from Aloe vera, which was known to have antioxidative activity, in a rat model of transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of middle cerebral artery for 2 hr with a silicone-coated 4-0 nylon monofilament in male Sprague-Dawley rats under isoflurane anesthesia Aloesin (1, 3, 10, 30 and 50 mg/kg/injection) was administered intravenously 3 times at 0.5, 2 and 4 hr after onset of ischemia. Neurological score was measured 24 hr after onset of ischemia immediately before sacrifice. Seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride and infarct size was measured using a computerized image analyzer. Treatment with the close of 1 or 50 mg/kg did not significantly reduce infarct volume compared with the saline vehicle-treated control group. However, treatments with the closes of 3 and 10 mg/kg significantly reduced both infarct volume and edema by approximately 47% compared with the control group, producing remarkable behavioral recovery effect. Treatment with the close of 30 mg/kg also significantly reduced infarct volume to a lesser extent by approximately 33% compared with the control group, but produced similar degree of behavioral recovery effect. In addition, general pharmacological studies showed that aloesin was a quite safe compound. The results suggest that aloesin can serve as a lead chemical for the development of neuroprotective agents by providing neuroprotection against focal ischemic neuronal injury.

• Journal of Life Science
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• v.24 no.8
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• pp.873-879
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• 2014

The constituents from the needles of the pine tree, Pinus densiflora, were purified and investigated for antithrombotic activity. The needles were initially extracted three times with 70% ethanol, and the extract was sequentially fractionated with chloroform and n-butanol. The aqueous layer formed after n-butanol fractionation was subjected to purification by medium pressure and high pressure liquid chromatography. The two neolignans, 2, 3-dihydro-7-hydroxyl-3-hydroxymethyl-2-(4'-hydroxyl -3-methoxyphenyl)-5-benzofuranpropanol-3-O-${\alpha}$-rhamnopyranoside (a neolignan glycoside) and 2, 3-dihyro-3-hydroxymethyl-7-methoxy-2-(4'-hydroxyphenyl-3'-methoxy)-5-benxofuran propanol 4'-O-${\alpha}$-rhamnopyranoside (icariside $E_4$) were identified by $^1H$ and $^{13}C$ NMR spectra. The effect of the purified compounds, the neolignan glycoside and icariside $E_4$ on thrombin inhibition were investigated by measuring thrombin clotting time in plasma. As a result, the clotting of the neolignan glycoside was delayed four times compared to that of icariside $E_4$. In addition, an analysis of the inhibition effect by changing the concentration showed that the clotting time was delayed in accordance with an increase in the concentration of the neolignan glycoside. Furthermore, we examined the interaction of thrombin and fibrinogen to clarify the action mechanism. As a result, the delay of clotting time in the response of thrombin and pure fibrinogen may indicate that neolignan glycosides inhibit the thrombin action in a direct manner, leading to the suppression of fibrin generation.