• Molecules and Cells
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• v.40 no.8
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• pp.567-576
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• 2017

The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.729-733
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• 1998

The crude extract of Streptomyces sp. strain KM86-9B, isolated from a marine sponge, displayed significant inhibition on topoisomerase I activity. Investigation of the ca usative components by bioactivity-directed fractionation resulted in the isolation of a series of iso- and anteiso-fatty acids.

• YAKHAK HOEJI
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• v.54 no.6
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• pp.466-473
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• 2010

A series of $3{\beta}$-substituted 5-androstene-$17{\beta}$-carboxamides were synthesized from analogs of $3{\beta}$-hydroxy-5-androstene-$17{\beta}$-carboxylic acid (1) with tert-butylamine, N,N-diethylamine and 3-aminopyridine and some compounds were epoxidized with mCPBA. A rat prostate testosterone $5{\alpha}$-reductase inhibitory activity of synthesized compounds was assessed by radioimmunoassay using [1,2,6,7-3H]-testosterone as substrate. All synthesized compounds showed lower activity than finasteride and the N-(3-pyridino)-$3{\beta}$-carboxycarbonyloxy-5-androstene-$17{\beta}$-carboxamide (12) showed weak inhibitory activity ($IC_{50}$: $2.4{\times}10^{-7}M$).

• Corrosion Science and Technology
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• v.15 no.4
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• pp.171-181
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• 2016

In this work, synergistic corrosion inhibition effect of nitrite and 3 kinds of ethanolamines on ductile cast iron using chemical and electrochemical methods was evaluated. This work attempts to clarify the synergistic effect of nitrite and ethanolamines. The effects of single addition of TEA, DEA, and MEA, and mixed addition of nitrite plus TEA, DEA or MEA on the corrosion inhibition of ductile cast iron in a tap water were evaluated. A huge amount of single addition of ethanolamine was needed. However, the synergistic effect by mixed addition was observed regardless of the combination of nitrite and triethanolamines, but their effects increased in a series of MEA + nitrite > DEA + nitrite > TEA + nitrite. This tendency of synergistic effect was attributed to the film properties and polar effect; TEA addition couldn't form the film showing high film resistance and semiconductive properties, but DEA or MEA could build the film having relatively high film resistance and n-type semiconductive properties. Moreover, it can be explained that this behaviour was closely related to electron attractive group within the ethanolamines, and thus corrosion inhibition power depends upon the number of the electron attractive group of MEA, DEA, and TEA.

• The Korean Journal of Pesticide Science
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• v.9 no.1
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• pp.23-25
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• 2005

3-Chloro-2-(4-chloro-2-fluoro-5-hydroxyphenyl)-4,5,6,7-tetrahydro-2H-indazole, which is the key intermediate of cyclic imide type compounds such as EK 5439 and S-275 series, were practically synthesized by the procedure of hydrolysis of by-products and were produced in the reaction of 2-(2-fluoro-4-chloro-5-hydroxyphenyl)-2,3a,4,5,6,7-hexahydroindazol-3-one with phosgene.

• The Korean Journal of Pesticide Science
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• v.5 no.3
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• pp.54-57
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• 2001

A series of bicyclic 4,5,6,7-tetrahydroindazole derivatives 6 have been synthesized, and their herbicidal activities were studied in flooded paddy condition. The compounds 6 showed herbicidal effects to barnyardgrass and Monochoria and good tolerance against rice at a rate of $0.063kg/ha{\sim}0.25kg/ha$.

• Bulletin of the Korean Chemical Society
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• v.32 no.5
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• pp.1650-1656
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• 2011

A series of potent tricyclic derivatives with a non-aromatic amide as potent PARP-1 inhibitors were successfully synthesized and their PARP-1 inhibitory activity was evaluated. Among the derivatives, 2-(1-propylpiperidin-4-yloxy)-7,8,9,10-tetrahydrophenanthridin-6(5H)-one 23c displayed potent activity in a PARP-1 enzymatic assay and cell-based assay ($IC_{50}$ = 0.142 ${\mu}M$, $ED_{50}$ = 0.90 ${\mu}M$) with good water solubility. Further, molecular modeling studies confirmed the obtained biological results.

• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1035-1038
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• 2009

Phytochemical investigation of the methanolic extract of Diospyros kaki leaves led to the isolation of osmanthuside H (1) and a new phenol glycoside, named gamnamoside [4-(3-hydroxypropyl)-2-methoxyphenol $\beta$-D-apiofuranosyl( 1 $\rightarrow$ 6)$\beta$-D-glucopyranoside] (2) along with (-) catechin (3) through a series of reversed phase column chromatography and preparative C18 HPLC. The structures of the isolates were determined by spectroscopic methods including IR, UV, HRTOFMS, and 2D NMR. Compounds 1, 2, and 3, showed good inhibitory activities ($IC_{50}$) of 175.4, 94.4, and 126.6 ${\mu}g/mL$ respectively, whereas a reversible ADH inhibitor, 4-methylpyrazole, showed the $IC_{50}$ of 326.6 ${\mu}g/mL$ against alcohol dehydrogenase (ADH).

• Journal of Life Science
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• v.27 no.2
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• pp.139-148
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• 2017

The inhibition of tyrosinase, a key enzyme in mammalian melanin synthesis, plays an important role in preventing skin pigmentation and melanoma. Therefore, tyrosinase inhibitors are very important in the fields of medicine and cosmetics. However, only a few tyrosinase inhibitors are currently available because of their toxic effects on skin or lack of selectivity and stability. Therefore, we synthesized a novel series of (E)-2-(substituted benzylidene)-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-one derivatives and evaluated their inhibitory effects on mushroom tyrosinase, with the aim of discovering a novel tyrosinase inhibitor. Among 19 derivatives, MHY3655 ($IC_{50}=0.1456{\mu}M$) showed the strongest inhibitory effect on tyrosinase activity compared to kojic acid ($IC_{50}=17.2{\mu}M$), a well-known tyrosinase inhibitor. In addition, MHY3655 showed competitive inhibition on Lineweaver-Burk plots. We confirmed that MHY3655 strongly interacts with mushroom tyrosinase residues through the docking simulation. Substitutions with a hydroxy group at both R2 and R4 in the phenyl ring indicated that these groups play a major role in the high binding affinity to tyrosinase. Further, MHY3655 did not show cytotoxicity at the concentrations tested in B16F10 melanoma cells. In conclusion, the novel compound MHY3655 potentially shows tyrosinase inhibitory activity, and it could be used as an ingredient in whitening cosmetics.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.5
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• pp.403-409
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• 2014

The Bis protein is known to be involved in a variety of cellular processes including apoptosis, migration, autophagy as well as protein quality control. Bis expression is induced in response to a number of types of stress, such as heat shock or a proteasome inhibitor via the activation of heat shock factor (HSF)1. We report herein that Bis expression is increased at the transcriptional level in HK-2 kidney tubular cells and A172 glioma cells by exposure to oxidative stress such as $H_2O_2$ treatment and oxygen-glucose deprivation, respectively. The pretreatment of HK-2 cells with N-acetyl cysteine, suppressed Bis induction. Furthermore, HSF1 silencing attenuated Bis expression that was induced by $H_2O_2$, accompanied by increase in reactive oxygen species (ROS) accumulation. Using a series of deletion constructs of the bis gene promoter, two putative heat shock elements located in the proximal region of the bis gene promoter were found to be essential for the constitutive expression is as well as the inducible expression of Bis. Taken together, our results indicate that oxidative stress induces Bis expression at the transcriptional levels via activation of HSF1, which might confer an expansion of antioxidant capacity against pro-oxidant milieu. However, the possible role of the other cis-element in the induction of Bis remains to be determined.