• Bulletin of the Korean Chemical Society
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• v.35 no.12
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• pp.3571-3575
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• 2014

Proteasome, a multicatalytic protease complex, has been validated as a promising therapeutic target in oncology. Carfilzomib (Kyprolis$^{(R)}$), a tetrapeptide epoxyketone, irreversibly inhibits the chymotrypsin-like (CT-L) activity of the proteasome and has been recently approved for multiple myeloma treatment by FDA. A chemistry effort was initiated to discover the compounds that are reversibly inhibit the proteasome by replacing the epoxyketone moiety of carfilzomib with a variety of ketones as reversible and covalent warheads at the C-terminus. The newly synthesized compounds exhibited significant inhibitory activity against CT-L activity of the human 20S proteasome. When the compounds were tested for cancer cell viability, 14-8 was found to be most potent in inhibiting Molt-4 acute lymphoblastic leukemia cell line with a $GI_{50}$ of $4.4{\mu}M$. Cytotoxic effects of 14-8 were further evaluated by cell cycle analysis and Western blotting, demonstrating activation of apoptotic pathways.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.41 no.6
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• pp.414-418
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• 2008

Volatile compounds in Omangdungi (Styela plicata)-Doenjang (soybean paste) stew were analyzed using solvent-assisted flavor evaporation/gas chromatography/mass-selective detection/olfactometry (SAFE/GC/MSD/O) and aroma extract dilution analysis (AEDA). The GC/O analysis detected 37 volatile compounds, of which 32 were positively identified, and included 9 aldehydes, 5 alcohols, 4 aromatic hydrocarbons, 4 ketones, 3 esters, 3 N-containing compounds, 2 acids, 1 S-containing compound, and 1 furan. Nine aroma-active odorants ($\log_3FD{\geq}3.0$) in the sample included six compounds derived from Doenjang (3-methyl(thio)propanal, tetramethylpyrazine, 4-vinyl-2-methoxyphenol, 2-acetylpyrrole, butyric acid, and 2-methoxyphenol) and three compounds from Omangdungi (2-acetyl-2-thiazoline, 9-decanol, and 6-decenol). Three compounds derived from Omangdungi (9-decanol, 6-decenol, and 6-nonenol) were thought to enhance the seafood-like flavor of Omangdungi-Doenjang stew.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4019-4023
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• 2016

Background: Colorectal cancer (CRC) or bowel cancer is one of the most important cancer diseases, needing serious attention. The cell surface receptor gene human epidermal growth factor receptor (EGFR) may have an important role in provoking CRC. In this pharmaceutical era, it is always attempted to identify plant-based drugs for cancer, which will have less side effects for human body, unlike the chemically synthesized marketed drugs having serious side effects. So, in this study the authors tried to assess the activity of two important plant compounds, ferulic acid (FA) and p-coumaric acid (pCA), on CRC. Materials and Methods: FA and pCA were tested for their cytotoxic effects on the human CRC cell line HCT 15 and also checked for the level of gene expression of EGFR by real time PCR analysis. Positive results were confirmed by in silico molecular docking studies using Discovery Studio (DS) 4.0. The drug parallel features of the same compounds were also assessed in silico. Results: Cytotoxicity experiments revealed that both the compounds were efficient in killing CRC cells on a controlled concentration basis. In addition, EGFR expression was down-regulated in the presence of the compounds. Docking studies unveiled that both the compounds were able to inhibit EGFR at its active site. Pharmacokinetic analysis of these compounds opened up their drug like behaviour. Conclusions: The findings of this study emphasize the importance of plant compounds for targeting diseases like CRC.

• Journal of Integrative Natural Science
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• v.6 no.3
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• pp.138-142
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• 2013

The HIV-1 envelope glycoprotein gp120 plays a vital role in the entry of the virus into the host cells. The crucial role of the glycoprotein suggests gp120 as potential drug target for the future antiviral therapies. Identification of the binding mode of small drug like compounds has been an important goal in drug design. In the current study we attempt to propose binding mode of indole derivatives in the binding pocket of gp120. These derivatives are reported to inhibit HIV-1 by acting as attachment inhibitors that bind to gp120 and prevent the gp120-CD4 interaction and thus inhibit the infectivity of HIV-1. To elucidate the molecular basis of the small molecules interactions to inhibit the glycoprotein function we employed the molecular docking simulation approach. This study provides insights to elucidate the binding pattern of indole-based gp120 inhibitors and may help in the rational design of novel HIV-1 inhibitors with improved potency.

• Journal of Yeungnam Medical Science
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• v.12 no.2
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• pp.405-411
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• 1995

Lichenoid drug eruption is lichenoid skin eruptions caused by certain drugs and compounds, and can be identical or similiar to lichen planus. A 75-year-old woman who had taken antituberculosis medication(INH, ethambutol, rifampin) for 4 months developed pruritic generalized erythematous papular eruptions on the trunk and extremities, alopecia and nail dystropy. Histopathologic findings were hyperkeratosis, hypergranulosis, hydrophic degenaration of basal layer, band like lymphohistiocytic infiltration in the upper dermis and perivascular lymphohistiocytic infiltration in the deep dermis. She was treated with systemic corticosteroid, and then skin lesion were slightly improved. After termination of antituberculosis medication, skin lesions were markedly improved with residual hyperpigmentation. Alopecia and nail dystrophy were also improved.

• Bulletin of the Korean Chemical Society
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• v.28 no.4
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• pp.561-566
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• 2007

Adenosine kinase (AK) is a ubiquitous intracellular enzyme, which catalyzes the phosphorylation of adenosine (ADO) to adenosine monophosphate (AMP). AK inhibitors have therapeutic potential as analgesic and antiinflammatory agents. A chemical feature based pharmacophore model has been generated from known AK inhibitors (26 training set compounds) by HypoGen module implemented in CATALYST software. The top ranked hypothesis (Hypo1) contained four features of two hydrogen-bond acceptors (HBA) and two hydrophobic aromatics (Z). Hypo1 was validated by 124 test set molecules with a correlation coefficient of 0.905 between experimental and estimated activity. It was also validated by CatScramble method. Thus, the Hypo1 was exploited for searching new lead compounds over 238,819 chemical compounds in NCI database and then the selected compounds were screened based on restriction estimated activity and Lipinski's rules to evaluate their drug-like properties. Finally we could obtain 72 new lead candidates and the two best compound structures from them were posted.

• The Korea Journal of Herbology
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• v.26 no.3
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• pp.37-45
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• 2011

Objectives : This study focused on Schisandrae Fructus (SF) and Perilae Folium (PF), traditional medicine herbs and health functional food in Korea, Japan and China. We investigated various pharmacological activities that include a potential source of free radical scavenging, anti-viral, anti-microbial, anti-allergy and anti-inflammatory activities. Methods : We conducted an investigation of total contents of phenolic and flavonoid compounds in these single herbal extraction with/without combined to mixture. We also measured antioxidant activities such as DPPH free radical scavenging, SOD-like scavenging, nitrite scavenging and hydroxyl radical scavenging activities, xanthine oxidase inhibition, linoleic acid peroxidation inhibition, and reducing power. Results : As the results, contents of total phenoilc compounds and flavonoids were higher in those of PF than those of SF. Those of SF+PF mixture showed the synergy effects compared with those of SF and PF single extractions. Activities of DPPH free radical and SOD-like scavenging in 1 mg/mL concentration increased in dose dependent manners. That of SF increased compared with that of PF. That of SF and PF mixture also increased compared with that of BHA as a positive control. The other antioxident activities also showed similar to patten of activity of DPPH free radical scavenging. When combined to SF and PF extractions, there was showed synergic effect compared with those of BHA, excepted activities of xanthine oxidase inhibition and reducing power. Taken together, SF and PF have high phenolic and flavonoid compounds content furthermore, antioxidant activities in SF and PF mixture showed more synergy effect compared with those of BHA. Conclusions : Therefore, these findings suggest that SF and PF mixture may offer functional materials potential for development of functional beverage. But further studies are needed for the identification of the active compounds.

• Bulletin of the Korean Chemical Society
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• v.34 no.7
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• pp.1972-1984
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• 2013

Microtubules play an important role in intracellular transport, mobility, and particularly mitosis. Paclitaxel (Taxol$^{TM}$) and paclitaxel-like compounds have been shown to be anti-tumor agents useful for various human tumors. Paclitaxel-like compounds operate by stabilizing microtubules through interface binding at the interface between two ${\beta}$-tubulin monomers in adjacent protofilaments. In this paper we present the elucidation of the structural features of paclitaxel and paclitaxel-like compounds (e.g., epothilones) with microtubule stabilizing activities, and relate their activities to spatial and chemical features of the molecules. CATALYST program was used to generate three-dimensional quantitative structure activity relationships (3D-QSARs) resulting in 3D pharmacophore models of epothilone- and paclitaxel-derivatives. Pharmacophore models were generated from diverse conformers of these compounds resulting in a high correlation between experimental and predicted biological activities (r = 0.83 and 0.91 for epothilone and paclitaxel derivatives, respectively). On the basis of biological activities of the training sets, five- and four-feature pharmacophore hypotheses were generated in the epothilone and paclitaxel series. The validation of generated hypotheses was achieved by using twelve epothilones and ten paclitaxels, respectively, which are not in the training sets. The clustering (grouping) and merging techniques were used in order to supplement spatial restrictions of each of hypothesis and to develop more comprehensive models. This approach may be of use in developing novel inhibitor candidates as well as contributing a better understanding of structural characters of many compounds useful as anticancer agents targeting microtubules.

• Journal of Pharmacopuncture
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• v.19 no.1
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• pp.7-15
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• 2016

Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the 'apicoplast', which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle's function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug resistance.

• Bulletin of the Korean Chemical Society
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• v.31 no.12
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• pp.3605-3610
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• 2010

In the present study, some quinoline derivatives have been synthesized like 8-methoxy-4-methyl-2-amino-(3'-chloro-2'-oxo-4'-substituted aryl-1'-azetidinyl)quinolines 8-12 and 8-methoxy-4-methyl-2-amino-(2'-substituted aryl-4'-oxo-1',3'-thiazolidin-3'-yl) quinolines 13-17 from 8-methoxy-4-methyl-2-(substituted arylidenyliminoamino)-quinolines 3-7. The structural assignments of these compounds were based on spectral (IR, $^1H$-NMR, Mass) and elemental (C, H, N) analysis. Further, these compounds were evaluated for antibacterial activity against various bacterial strains. Three compounds 10, 11 and 16 were found to exhibit potent antibacterial activity as compared to the standard drug amphicillin.