• Journal of Life Science
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• v.30 no.1
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• pp.96-105
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• 2020

Sirtuin inhibitors are pharmaceutically and therapeutically valuable compounds that inhibit sirtuin, a type III histone deacetylase. Synthetic sirtuin inhibitors were discovered and characterized using cell-based screens in yeast (Saccharomyces cerevisiae) and have been used in the study of aging, carcinogenesis, and diabetes, all of which are related to sirtuin function. For medical applications, synthetic inhibitors have been further developed for increased potency and specificity, including compounds containing nicotinamide, thioacetyl lysine, β-naphthol, and indole derivatives. Suramin, tenovin, and their analogues were developed as a result. Sirtuin inhibitors were found to affect organic development and have been used to genetically modify plants, although a sirtinol-resistant mutation in the biosynthesis of a molybdopterin cofactor for an aldehyde oxidase has been identified. Some natural flavonoids, and catechin and quercetin derivatives also act as sirtuin inhibitors have been studied to identify a more potent inhibitor for therapeutic purposes. In this review, sirtuin is introduced and the therapeutic inhibitors that have been developed are presented, particularly sirtinol which has been used for genetic modification in plants though it was not designed to be so. Sirtuin inhibitors with greater potency and selectivity are required and those developed in pharmaceutics should be used in plant research to identify more authentic sirtuins in plants.

• Korean Journal of Agricultural Science
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• v.39 no.1
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• pp.69-73
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• 2012

The purpose of this study was to evaluate the potential of naturally occurring aldose reductase (AR) inhibitors from white-color natural products (Aruncus dioicus var. kamtschaticus, Chionanthus retusa, Cosmos bipinnatus, Hibiscus syriacus, Hydrangea paniculata, Magnolia denudata, Prunus padus, Robinia pseudo-accacia, Rhododendron mucronulatum for. albiflorum, Spiraea blumei, and Spiraea prunifolia var. simpliciflora). The MeOH extract of white-color natural products were tested on rat lens AR inhibition in vitro. Among them, the MeOH extract of R. mucronulatum for. albiflorum showed highest inhibition on AR ($IC_{50}$ value, 1.07 ${\mu}g/ml$). These results suggested that R. mucronulatum for. albiflorum, a white-color natural product, could be a useful resource in the development of a novel AR inhibitory agent against diabetic complications.

• Natural Product Sciences
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• v.2 no.2
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• pp.123-129
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• 1996

Chemical carcinogenesis is associated with the increase of intracellular polyamine levels, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse epidermal ODC activity are essential to skin tumor promotion by TPA. Therefore, for the discovery of new cancer chemopreventive agents, we have evaluated about 73 kinds of natural products to study inhibitory effects against ODC activity induced by TPA in T24 cell culture system. The total methanol extracts of plants fractionated into three layers (hexane, ethyl acetate and water layer) were tested and the hexane fraction of Angelica gigas $(root\;bark,\;IC_{50}:\;7.4\;{\mu}g/ml)$ and the ethyl acetate fraction of Corydalis ternata $(root,\;IC_{50}:\;7.5\;{\mu}g/ml)$ were the most effective on the inhibition of TPA-induced ODC activity, These active fractions are under investigation with further sequential fractionation using column chromatography.

• 한국약용작물학회:학술대회논문집
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• 2008.11a
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• pp.265-266
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• 2008

• Journal of Microbiology and Biotechnology
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• v.10 no.4
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• pp.544-546
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• 2000

Grb2 is an important adaptor protein in the mitogenic Ras signaling pathway of receptor tyrosine kinases, and contains one SH2 domain and two SH3 domains. The SH2 domain binds to specific phosphotyrosine motifs on receptors or adaptor proteins such as Shc. The SH2 domain antagonists may lead to blocking of the oncogenic Ras signals and to developing new antitumor agents. In the course of screening SH2 antagonists from natural sources, cslerotiorin (1) and isochromophilone IV (2) were isolated from a strain, Penicillium multicolor F1753, and their structures were established by NMR spectral data. The metabolites significantly inhibited the binding between the Grb2-SH2 domain and phosphopeptide derived from the Shc protein, with $IC_{50}$ values of $22{\;}\mu\textrm{M}{\;}and{\;}48{\;}\mu\textrm{M}$ for (1) and (2), respectively. The compounds are the first nonpeptidic inhibitors of the SH2 domain from a natural source.

• Bulletin of the Korean Chemical Society
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• v.35 no.6
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• pp.1763-1768
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• 2014

In the course of our program to search for antithrombotic and anti-inflammatory agents from plants, twelve phenolics (1-12) were isolated from the stems of Parthenocissus tricuspidata. Their structures were elucidated on the basis of spectroscopic (1D and 2D NMR, and MS) data analyses, and comparison with published data. At the concentration of $100{\mu}g/ml$, compounds 2, 4, 6 and 10 possessed potential effects on anti-blood coagulation, with inhibitory percentage of 216, 174, 148 and 225%, respectively; while aspirin used as positive control showed 181% inhibition at the same concentration. Furthermore, the anti-inflammatory activity of isolated compounds (1-12) was investigated on lipopolysaccharide (LPS)-induced murine macrophage cells (RAW264.7). Compounds 2, 4 and 6 also potential inhibited the production of nitric oxide, with $IC_{50}$ values of $11.9{\pm}0.3$, $2.9{\pm}0.2$ and $29.0{\pm}0.6{\mu}M$, respectively. Celastrol, the positive control used, gave an $IC_{50}$ value of $1.0{\pm}0.1{\mu}M$.

• YAKHAK HOEJI
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• v.41 no.2
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• pp.153-160
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• 1997

One hundred and seventy crude drugs were screened for prolyl endopeptidase (PEP) inhibitors. Among them, 80% methanolic extract of 18 medicinal plants such as Polygonum cuspi data, Sanguisorba officinalis, Eugenia caryophyllata, Rubus coreanus, Cinnamomum cassia (Cassiae Cortex and Cinammomi Ramulus), Rheum palmatum, Ulmus pumila, Sorbus commixta, Areca catechu, Uncaria sinensis, Terminalia chebula, Caesalpinia sappan, Nelumbo nucifera, Machilus thunbergii, Paeonia moutan, Elscholtzia patrini and Cynomorium coccineum inhibited more than 70% of PEP activity at a concentration of 40 ppm. The active principles of P. moutan, M. thunbergii, T chebula, A. catechu, S. commixta, R. palmatum, R. coreanus, E. caryophyllata and P. cuspidata were transferred into organic solvents, which showed more than 75% inhibition at 5 ppm.

• Molecules and Cells
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• v.21 no.2
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• pp.294-301
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• 2006

We have previously reported that phosphorylation of eukaryotic elongation factor 2 (eEF2) is related to the differentiation of chick embryonic muscle cells in culture. In the present study, we found that eEF2 phosphorylation declined shortly after induction of differentiation of L6 myoblasts, when the cells prepare for terminal differentiation by withdrawing from the cell cycle. This decrease in phosphorylation was prevented by inhibitors of phosphoinositide 3-kinase (PI3-kinase) that strongly inhibit myoblast differentiation. We hypothesized that PI3-kinase plays an important role in myoblast differentiation by regulating eEF2 phosphorylation in the early stages of differentiation. To test this hypothesis, myoblasts were synchronized at in $G_2/M$ and cultured in fresh differentiation medium (DM) or growth medium (GM). In DM the released cells accumulated in $G_0$/$G_1$ while in GM they progressed to S phase. In addition, cyclin D1 was more rapidly degraded in DM than in GM, and eEF2 phosphorylation decreased more. Inhibitors of PI3-kinase increased eEF2 phosphorylation, but PI3-kinase became more activated when eEF2 phosphorylation declined. These results suggest that the regulation of L6 myoblast differentiation by PI3-kinase is related to eEF2 phosphorylation.

• Natural Product Sciences
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• v.26 no.4
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• pp.345-350
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• 2020

In recent years, tyrosine kinases (TKs) have been the target to combat cancers, and most of the developed inhibitors are of synthetic origin. Natural compounds that have the properties as the TK's inhibitors are very limited. This paper described the isolation of a new dammarane triterpene from the tree bark of Sandoricum koetjape, along with three known related dammaranes from the damar resin of Shorea javanica, as well as their inhibitory properties against eight receptor TKs (RTKs: EGFR, HER2, HER4, IGF1R, InsR, KDR, PDGFRα, and PDGFRβ). Based on the NMR and mass spectral data the new compound was identified as (12β,20S)-12,20-dihydroxy-3,4-seco-dammaran-4,24-dien-3-oic acid (12β-hydroxydammarenolic acid) (1), while the three known compounds were identified as (20S)-20-hydroxy-3,4-seco-dammaran-4,24-dien-3-oic acid (dammarenolic acid) (2), (3β,20S)-3,20-dihydroxydammaran-24-ene (3), and (20S)-3-oxo-20-hydroxydammaran-24-ene (4). The tyrosine kinase assay of the four compounds resulted only 1 and 2 at concentration of 10 μM that had weak activity against EGFR and InsR, with their % inhibitory were 30%, 27% (1), 45%, and 32% (2), respectively. The results suggested that the presence of a linear carboxylic acid group in both compounds could be of significance to the inhibitory properties against the two RTKs.

• Journal of dental hygiene science
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• v.24 no.2
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• pp.84-96
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• 2024

Background: Recent studies have elucidated the quorum-sensing mechanisms, biofilm formation, inter-pathogen interactions, and genes related to oral pathogens. This review aims to explore the recent expansion of drug targets against oral pathogens and summarize the current research on novel antibiotic substances derived from marine organisms that target oral pathogens. Methods: A comprehensive literature review summarized the novel mechanisms pertaining to quorum-sensing signal transmission systems, biofilm formation, and metabolite exchange in oral pathogens. The amino acid sequences of the 16 proteins identified as potential drug targets were systematically classified and compared across various oral microorganisms. Results: Through a literature review, we identified nine studies researching quorum sensing signaling inhibitors targeting oral pathogens. A comparison of the amino acid sequences of 16 potential drug targets in oral microorganisms revealed significant differences between oral pathogens and beneficial oral symbiotic microorganisms. These findings imply that it is possible to design drugs that can bind more selectively to oral pathogens. Conclusion: By summarizing the results of recent research on the signaling mechanisms that cause pathogenicity, new drug targets against oral pathogens were proposed. Additionally, the current status of developing new antibiotics for oral pathogens using recently developed quorum sensing inhibitors and natural products derived from marine organisms was introduced. Consequently, marine natural products can be used to develop drugs targeting new proteins in oral pathogens.