• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1212-1220
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• 2013

The human coagulation factor XI (FXI) is a serine protease that plays a significant role in blocking of the blood coagulation cascade as an attractive antithrombotic target. Selective inhibition of FXIa (an activated form of factor XI) disrupts the intrinsic coagulation pathway without affecting the extrinsic pathway or other coagulation factors such as FXa, FIIa, FVIIa. Furthermore, targeting the FXIa might significantly reduce the bleeding side effects and improve the safety index. This paper reports on a docking-based three dimensional quantitative structure activity relationship (3D-QSAR) study of the potent FXIa inhibitors, the chloro-phenyl tetrazole scaffold series, using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods. Due to the characterization of FXIa binding site, we classified the alignment of the known FXIa inhibitors into two groups according to the docked pose: S1-S2-S4 and S1-S1'-S2'. Consequently, highly predictive 3D-QSAR models of our result will provide insight for designing new potent FXIa inhibitors.

• Archives of Pharmacal Research
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• v.29 no.6
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• pp.459-463
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• 2006

Previous studies on the anticonvulsant activity of $N-Cbz-{\alpha}-aminoglutarmides$ have shown that the derivatives of $N-Cbz-{\alpha}-amino-N-alkoxy$ glutarimide have significant anticonvulsant activity. In addition, their anticonvulsant activities are dependent on the presence of N-alkoxy groups. Based on these results, a series of $N-Cbz-{\alpha}-amino-glutarimidooxy$ carboxylates derivatives (3a-e) were synthesized in moderate yield using a known synthetic procedure. Their anticonvulsant activities were evaluated using the maximal electroshock seizure (MES) test, the pentylene tetrazole induced seizure (PTZ) test, and the strychinine (Str) threshold test with the ultimate aim of developing more active anticonvulsants. None of the compounds (3a-e) tested showed anticonvulsant activity in the MES and PTZ test. However, all the compounds tested exhibited significant anticonvulsant activity in the Str. test. The most active compound in the Str. test was the methyl ester of $N-Cbz-{\alpha}-amino-glutarimidooxy$ acetic acid 3a $(ED_{50}\;=\;42.9\;mg/kg)$.

• Journal of the Korean Society of Propulsion Engineers
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• v.23 no.5
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• pp.53-59
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• 2019

Solid fuel reacts with an oxidizer during combustion of a propellant to increase performance. Representative solid fuels are aluminum, cyclotrimethylenetrinitramine (RDX) and octahydro-1, 3,5,7-tetra nitro-1,3,5,7-tetrazocin (HMX). During combustion, these compounds generate white smoke by reacting with moisture and produce materials that are harmful to the environment, such as carbon monoxide, carbon dioxide, and methane gas. This study prepared a high-nitrogen-containing energetic material, hydrazinium 5-aminotetrazolate (HAT), which could be applied as a solid fuel. The compound was characterized by nuclear magnetic resonance (NMR) spectroscopy, and a thermal analysis was measured by differential scanning calorimetry (DSC). Also, the specific impulses and volumes of detonation gases were calculated using the EXPLO5 program.

• YAKHAK HOEJI
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• v.42 no.1
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• pp.12-24
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• 1998

For the development of new cephalosporin antibiotics with aminothiazolcarboxymethylethoxyimino moiety on the C-7 position and tetrazolymethyl moiety on the C-3 position of cephe m ring, 7${\beta}$-[(Z)-2-(2-aminothiazol-4-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[5-(substituted)tetrazol-2-yl]methyl-3-cephem-4-carboxylic acids(28-35) were synthesized. These compounds were tested for antimicrobial activity in vitro against Gram(+) and Gram(-) bacteria. They showed remarkable antibacterial activity against Escherichia coli AB 1157, Escherichia coli AB 0111, Escherichia coli BE 1186, Micrococcus luteus ATCC 9341, Salmonella typhimurium TV 119, Salmonella typhimurium SL 1102, Staphylococcus aureus IFO 12732, Staphylococcus aureus R-209, but these compounds were not active against Pseudomonas aeruginosa N-10.

• Korean Journal of Medicinal Crop Science
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• v.27 no.6
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• pp.365-375
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• 2019

Background: Oxidative stress plays an important role in neuro-degenerative disorders such as Alzheimer's disease. Oxidative stress is mediated by reactive oxygen species (ROS), which are implicated in the pathogenesis of numerous diseases, and account for the toxicity of a wide range of compounds. Methods and Results: In order to study the neuro-protective effect of the complex extracts of Aster scaber Thunberg (AS) and Chaenoleles sinensis Koehne (CSK) against hydrogen peroxide in PC12 cells, cell viability was evaluated by the MTT assay using tetrazole, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and the intracellular ROS levels were determined the by 2',7'-dichlorofluorescein diacetate (DCF-DA) assay. In order to examine the anti-amnesic effects of the complex extracts of AS and CSK, behavioral tests were performed on male ICR mice. The ameliorating effect of the complex extracts against Aβ_1-42-induced learning and memory impairment was analyzed by y-maze and passive avoidance tests. The AS and CSK extracts showed neuro-protective activity both in vitro and in vivo, and the neuro-protective effect of their 60 : 40 (AS : CSK) mixture was better than that of the other mixtures. Moreover, the complex extracts synergistically inhibited acetylcholinesterase activity and rapid peroxidation. Conclusions: A mixture of the AS and CSK extracts could be used to develop functional foods and serve as raw materials for the development of therapeutics against Alzheimer's disease.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6073-6076
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• 2012

Discovery of anticancer drugs that kill or disable tumor cells in the presence of normal cells without undue toxicity is a potential challenge for therapeutic care. Several papers in the literature have emphasized the potential implications of marine products such as seaweeds which exhibit antitumor activity. Study attempts to screen the antitumor effect of Sargassum sp, against chosen cell lines such as MCF-7 (Breast cancer) and Hep-2 (Liver Cancer). Ethanol extract of Sargassum sp. was concentrated using a Soxhlet apparatus and dissolved in DMSO. In vitro cytotoxic activity of Sargassum sp at various concentrations ($100{\mu}g/ml-300{\mu}g/ml$) screened for antitumor effect against the chosen cell lines using MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole). The study documented that the percentage of cell viability has been reduced with increased concentration, as evidenced by cell death. Sargassum sp extract shows potential cytotoxic activity ($P{\leq}0.05$) with $IC_{50}$ of $200{\mu}g/ml$ and $250{\mu}g/ml$ against Hep-2 and MCF-7 cell lines respectively. The ethanol fraction of Sargassum sp induced cell shrinkage, cell membrane blebbing and formation of apoptotic bodies with evidence of bioactive components as profound influencing factors for anti-tumor effects. Further research need to be explored for the successful application of Sargassum sp as a potent therapeutic tool against cancer.

• Korean Journal of Environmental Agriculture
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• v.15 no.4
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• pp.501-505
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• 1996

Azimsulfuron [1H-pyrazole-5-sulfonamide,N-(((4,6-dimethoxy-pyridine-2-yl-aminocarbonyl-4-(2-methyl-2H-tetrazole-5-yl)] is a new sulfonamide herbicide that selectively controls a wide range of weeds in lowland rice (Oryza sativa). It effectively controlled Cyperus serotinus, Eleocharis kuroguwai, Sagittaria pygmaea, S. trifolia, and Scirpus juncoides at 7.5 - 30 g ai/ha. In the tolerance test on grasses carried out in a nutrient solution containing 0.3 - 30 ppm of azimsulfuron, greater inhibition occurred in roots of both rice and barnyardgrass (Echinochloa crus galli) than in shoots. However, rice root was approximately 5-fold more tolerant than that of barnyardgrass. The downward movements as determined by 50% growth inhibition of S. juncoides were 4-cm in clay loam and 6.5-cm in sandy loam soil with 3-cm/day leaching for 3 days. When incubated at 20 and $30^{\circ}C$, the residual effect in clay loam soil lasted for 30 and 21 days, respectively. In a soil column applied at 15 g ai/ha of azimsulfuron followed by 3-cm/day leaching for 3 days, dry weights of S. trifolia emerging at 5, 10, and 15-cm depth were reduced to 87, 85, and 79% of the corresponding untreated control, respectively. Susceptibility of S. trifolia to azimsulfuron did not greatly vary with the emergence depth.

• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.696-700
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• 2009

Purpose : We screened more than 350 compounds with an endoperoxide ring structure in search of an anti-leukemic drug and found that compound 127 (c-127) could induce significant cytotoxicity in HL-60 cells. In this study, we investigated the molecular mechanisms of compound 127-induced antitumor activity on HL-60 cells. Methods : HL-60 cells were cultured in Rosewell Park Memorial Institute 1640 and cell viability was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], a tetrazole assay. Apoptosis was assessed by a DNA fragmentation test. Apoptotic machineries were determined by Western blot analysis. Results : C-127 could induce a cytotoxic effect at 24 h and apoptosis at 6 h, which was demonstrated with MTT assay and DNA fragmentation test, respectively. The apoptotic effect of this drug was caused by the activation of the intracellular caspase-8,3 activation, the cleavage of pro-apoptotic Bid, and the increase of c-Jun expression accompanied with JNK (Jun N-terminal kinases) phosphorylation. On the contrary, it increased the expression of anti-apoptotic Bcl-2 levels, leading to the induction of the induction of anti-apoptotic effect. Taken together, the present study demonstrated that c-127 was a potent inducer of cytotoxicity on HL-60 cells through apoptotic mechanisms, which included the activation of caspase family, the regulation of Bcl-2 family, and the activation of JNK signaling pathway. Conclusion : Our results suggest that c-127 has a strong antitumor activity through the regulation of various apoptotic machineries on HL-60 cells. The compound may be utilized as an effective and potentially therapeutic drug in leukemia.

• Preventive Nutrition and Food Science
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• v.15 no.2
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• pp.137-142
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• 2010

Previous studies report that organo-sulfur compounds derived from garlic inhibited smooth muscle cell (SMC) proliferation and induced apoptosis of cancer cells. Recently, lipid-soluble compounds such as diallyl sulfides (DAS) and diallyl disulfides (DADS) have been reported to more effectively suppress tumor cell proliferation. However, there were few studies on the suppressive effects of lipid-soluble garlic sulfur compounds on the proliferation and migration of vascular smooth muscle cells (VSMC). Therefore, this study investigated the effect of DAS and DADS on VSMC proliferation/migration induced by oleic acid (OA), a principal fatty acid in circulating triglyceride of blood stream. Assays performed include a tetrazole (MTT) assay, a wound healing assay and a Western blots. VSMC proliferations were enhanced by OA in a dose-dependent manner at concentrations of $10{\sim}50\;{\mu}M$ and inhibited by DAS and DADS compared to non-treated control. OA-induced proliferations were also attenuated by DAS and DADS. OA-induced cell migrations were 2.5 times higher than non-treated control, and they were significantly attenuated by DAS (32% at $150\;{\mu}M$ and 50% at $200\;{\mu}M$) and DADS (40% at $150\;{\mu}M$ and 46% at $200\;{\mu}M$). OA-induced cell migration was also attenuated by PD98059 (ERK inhibitor), SB203580 (P38 inhibitor) and particularly by LY204002 (PI3K inhibitor) and SP600125 (JNK2 inhibitor). Additionally, Western blot assays showed that OA-induced JNK1/2-phosphorylation was down-regulated after treatment with DAS and DADS. In conclusion, the findings of our study support the idea that DAS and DADS may have a suppressive effect on the proliferation and migration of OA-induced VSMC and that this effect may be partly associated with PI3K and JNK2 pathways.

• Molecules and Cells
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• v.38 no.12
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• pp.1037-1043
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• 2015

The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. 1 TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-$phosphoelF2{\alpha}$-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance.