• The Korean Journal of Pesticide Science
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• v.11 no.3
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• pp.138-143
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• 2007

The relationships between three dimensional quantitative structure and activity relationships (3D-QSARs) for the selective fungicidal function between N-phenyl substituents of N-phenyl-O-phenyl-thionocarbamate derivatives analogues and their the fungicidal activities against resistant (RBC) and sensitive (SBC) gray mold (Botrytis cinerea) were studied quantitatively using CoMFA and CoMSIA methods. The statistical values of optimized CoMSIA (M7) model were better ($r^2$ & $q^2=CoMSIA{\gg}CoMFA$) than that of CoMFA (M5) model. And the factor influencing of the selective between the fungicidal activity against RBC and SBC was dependent on electrostatic field of CoMFA (M5) model. Therefore, it is predicted that, from the CoMSIA contour maps of CoMSIA (M7) model, the selectivity will be improved by the H-bond donor that is with negatively charged favored group at meta-position on the N-phenyl ring.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1885-1895
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• 2020

Rumex japonicus Houtt (RJH) is a valuable plant used in traditional medicine to treat several diseases, such as scabies and jaundice. In this study, Jurkat cell growth inhibitory extracts of R. japonicus roots were subjected to bioassay-guided fractionation, resulting in the isolation of three naphthalene derivatives (3-5) along with one anthraquinone (6) and two phenolic compounds (1 and 2). Among these compounds, 2-methoxystypandrone (5) exhibited potent anti-proliferative effects on Jurkat cells. Analysis by flow cytometry confirmed that 2-methoxystypandrone (5) could significantly reduce mitochondrial membrane potential and promote increased levels of mitochondrial reactive oxygen species (ROS), suggesting a strong mitochondrial depolarization effect. Real-time quantitative polymerase chain reaction (qPCR) analysis was also performed, and the results revealed that the accumulation of ROS was caused by reduced mRNA expression levels of heme oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, 2-methoxystypandrone (5) triggered strong apoptosis that was mediated by the arrest of the G0/G1 phase of the cell cycle. Furthermore, 2-methoxystypandrone (5) downregulated p-IκB-α, p-NF-κB p65, Bcl2, and Bcl-xl and upregulated BAX proteins. Taken together, these findings revealed that 2-methoxystypandrone (5) isolated from RJH could potentially serve as an early lead compound for leukemia treatment involving intracellular signaling by increasing mitochondrial ROS and exerting anti-proliferative effects.

• Journal of Applied Biological Chemistry
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• v.65 no.3
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• pp.195-202
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• 2022

Soybean (Glycine max L.) leaves have been researched as functional food stuff actively, but there is no validation method to control quality of soybean leaves (SL). In this study, we annotated seven kaempferol derivatives to confirm camelliaside A as index metabolite in SL using UHPLC-ESI-TOF-MS. HPLC-UVD validation method of camelliaside A in hot-water extract of SL was established according to validation guideline of functional foods from the Ministry of Food and Safety of Korea. The HPLC-UVD method was validated with reliable parameters for examining specificity, accuracy, precision, limit of detection and quantification and linearity. The established method gave the suitable ranges to qunatitate camelliaside A from the hot-water extract of soybean leaves.

• Mycobiology
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• v.51 no.1
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• pp.49-59
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• 2023

Antrodia cinnamomea, an edible and medicinal fungus with significant economic value and application prospects, is rich in terpenoids, benzenoids, lignans, polysaccharides, and benzoquinone, succinic and maleic derivatives. In this study, the transcriptome of A. cinnamomea cultured on the wood substrates of Cinnamomum glanduliferum (YZM), C. camphora (XZM), and C. kanehirae (NZM) was sequenced using the high-throughput sequencing technology Illumina HiSeq 2000, and the data were assembled by de novo strategy to obtain 78,729 Unigenes with an N50 of 4,463 bp. Compared with public databases, about 11,435, 6,947, and 5,994 Unigenes were annotated to the Non-Redundant (NR), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genome (KEGG), respectively. The comprehensive analysis of the mycelium terpene biosynthesis-related genes in A. cinnamomea revealed that the expression of acetyl-CoA acetyltransferase (AACT), acyl-CoA dehydrogenase (MCAD), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), mevalonate pyrophosphate decarboxylase (MVD), and isopentenyl diphosphate isomerase (IDI) was significantly higher on NZM compared to the other two wood substrates. Similarly, the expression of geranylgeranyltransferase (GGT) was significantly higher on YZM compared to NZM and XZM, and the expression of farnesyl transferase (FTase) was significantly higher on XZM. Furthermore, the expressions of 2,3-oxidized squalene cyclase (OCS), squalene synthase (SQS), and squalene epoxidase (SE) were significantly higher on NZM. Overall, this study provides a potential approach to explore the molecular regulation mechanism of terpenoid biosynthesis in A. cinnamomea.

• Korean Journal of Microbiology
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• v.41 no.3
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• pp.216-224
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• 2005

Chromatography has now been used successfully to provide the requisite purity for human plasma-derived biop-harmaceuticals such as coagulation factors and immunoglobulins. Recently, increasing attention has been focused on establishing efficient cleaning procedures to prevent potential contamination by microorganisms as well as carry-over contamination from batch to batch. The purpose of present study was to develop a cleaning validation system for the assurance of virus removal and/or inactivation during chromatography process. In order to establish an assay system for the validation of virus clearance during chromatography cleaning process, a quantitative real-time PCR method for porcine parvovirus(PPV) was developed, since PPV, a model virus for human parvovirus B19, has a high resistance to a range of physico-chemical treatment. Specific primers for amplification of PPV DNA was selected, and PPV DNA was quantified by use of SYBR Green I. The sensitivity of the assay was calculated to be 1.5 $TCID_{50}/ml$. The established real-time PCR assay was successfully applied to the validation of PPV removal and cleaning during SP-Sepharose cation chromatography for thrombin purification and Q-Sepharose anion chromatography for factor VIII purification. The comparative results obtained by real-time PCR assay and infectivity titrations suggested that the real-time PCR assay could be a useful method for chromatography cleaning validation and that it could have an additive effect on the interpretation and evaluation of virus clearance during the virus removal process.

• Applied Biological Chemistry
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• v.47 no.4
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• pp.414-421
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• 2004

3D QSAR studies for protox inhibition activities against root and shoot of the rice plant (Orysa sativa L.) and barnyardgrass (Echinochloa crus-galli) by a series of new 1-(5-methyl-3-phenylisoxazolin-5-yl)methoxy-2-chloro-4-fluorobenzene derivatives were conducted based on the results (Sung, N. D. et al.'s, (2004) J. Korean Soc. Appl. Biol. Chem. 47(3), 351-356) using comparative molecular similarity indices analysis (CoMSIA) methodology. Four CoMSIA models, without hydrogen bond donor field for the protox inhibition activities against root and shoot of the two plants, were derived from the combination of several fields using steric field, hydrophobic field, hydrogen bond acceptor field, LUMO molecular orbital field, dipole moment (DM) and molar refractivity (MR) as additional descriptors. The predictabilities and fitness of CoMSIA models for protox inhibition activities against barnyard-grass were higher than that of rice plant. The statistical results of these models showed the best predictability of the protox inhibition activities against barnyard-grass based on the cross-validated value $r^2\;_{cv}\;(q^2=0.635{\sim}0.924)$, non cross-validated, conventional coefficient $r^2\;_{ncv.}$ value $(r^2=0.928{\sim}0.977)$ and PRESS value $(0.255{\sim}0.273)$. The protox inhibition activities exhibited a strong correlation with the steric $(5.4{\sim}15.7%)$ and hydrophobic $(68.0{\sim}84.3%)$ factors of the molecules. Particularly, the CoMSIA models indicated that the groups of increasing steric bulk at ortho-position on the C-phenyl ring will enhance the protox inhibition activities against barnyard-grass and subsequently increase the selectivity.

• The Korean Journal of Pesticide Science
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• v.8 no.3
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• pp.151-161
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• 2004

Three dimensional quantitative structure-activity relationships (3D-QSAR) studies for the protox inhibition activities against root and shoot of rice plant (Orysa sativa L.) and barnyardgrass (Echinochloa crus-galli) by a series of new A=3,4,5,6-tetrahydrophthalimino, B=3-chloro-4,5,6,7-tetrahydro-2H-indazolyl and C=3,4-dimethylmaleimino group, and R-group substituted on the phenyl ring in 1-(5-methyl-3-phenylisoxazolin-5-yl)methoxy-2chloro-4-fluorobenzene derivatives were performed using comparative molecular field analyses (CoMFA) methodology with Gasteiger-Huckel charge. Four CoMFA models for the protox inhibition activities against root and shoot of the two plants were generated using 46 molecules as training set and the predictive ability of the each models was evaluated against a test set of 8 molecules. And the statistical results of these models with combination (SIH) of standard field, indicator field and H-bond field showed the best predictability of the protox inhibition activities based on the cross-validated value $r^2_{cv.}$ $(q^2=0.635\sim0.924)$, conventional coefficient $(r^2_{ncv.}=0.928\sim0.977)$ and PRESS value $(0.091\sim0.156)$, respectively. The activities exhibited a strong correlation with steric $(74.3\sim87.4%)$, electrostatic $(10.10\sim18.5%)$ and hydrophobic $(1.10\sim8.30%)$ factors of the molecules. The steric feature of molecule may be an important factor for the activities. We founded that an novel selective and higher protox inhibitors between the two plants may be designed by modification of X-subsitutents for barnyardgrass based upon the results obtained from CoMFA analyses.

• The Korean Journal of Pesticide Science
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• v.9 no.1
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• pp.26-34
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• 2005

3D-QSAR studies for the fungicidal activities against resistance phytophthora blight (RPC; 95CC7303) and sensitive phytophthora blight (Phytopthora capsici) (SPC; 95CC7105) by a series of new 2-alkoxyphenyl-3-phenylthioisoindoline-1-one derivatives (A & B) were studieded using comparative molecular similarity indices analyses (CoMSIA) methodology. From the based on the results, the two CoMSIA models, R5 and S1: as the best models were derivated. The statistical results of the models showed the best predictability and fitness for the fungicidal activities based on the cross- validated value ($q^2=0.714{\sim}0.823$) and non cross-validated, value ($r^2_{ncv.}=0.918{\sim}0.954$), respectively. The model R5 for fungicidal activity of RPC generated from the field fit alignment and combination of electrostatic field, H-bond acceptor field and LUMO molecular orbital field. The model S1 (or S5) for fungicidal activity of SPC generated from the atom based fit alignment and combination of steric field and HOMO molecular orbital field. The models also shows that inclusion of H-bond acceptor field (A) improved the statistical significance of the models. From the based graphical analyses of CoMSIA contribution maps, it was revealed that the novel selective character for fungicidal activities between the two fungi by modify of X-sub-stituent on the N-phenyl group and R-substituent on the S-phenyl group will be able to achivement.

• Applied Biological Chemistry
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• v.51 no.3
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• pp.171-176
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• 2008

The comparative molecular similarity indices analysis (CoMSIA) models between 3${\beta}$-Hydroxy-12-oleanen-28-oic acid (1-30) analogues as substrate molecule and their inhibitory activities ($pI_{50}$) against protein tyrosine phosphatase (PTP)-1B were derived and discussed quantitatively. Listing in order, the CoMFA>CoMSIA${\geq}$HQSAR>2D-QSAR model, these QSAR models had the better statistical values. The optimized CoMSIA F1 model at grid 3.0${\AA}$ had the best predictability and fitness ($q^2$=0.754 and $r^2$=0.976) by field fit alignment. The order of contribution ratio (%) of CoMSIA fields concerning the inhibitory activities was a H-bond acceptor (48.9%), steric field (25.8%) and hydrophobic field (25.4%), respectively. Therefore, the inhibitory activities of substrate molecules against PTP-1B were dependent upon H-bond acceptor field (A) of $R_4$-group. From the analytical results of CoMSIA contour maps, oleanolic acid derivatives will have better inhibition activities if $R_1$ group has H-bond acceptor disfavor, $R_3$group has steric disfavor and $R_4$ group has steric, hydrophobic, H-bond favor.

• Molecules and Cells
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• v.42 no.6
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• pp.480-494
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• 2019

Aggregates of disease-causing proteins dysregulate cellular functions, thereby causing neuronal cell loss in diverse neurodegenerative diseases. Although many in vitro or in vivo studies of protein aggregate inhibitors have been performed, a therapeutic strategy to control aggregate toxicity has not been earnestly pursued, partly due to the limitations of available aggregate models. In this study, we established a tetracycline (Tet)-inducible nuclear aggregate (${\beta}23$) expression model to screen potential lead compounds inhibiting ${\beta}23$-induced toxicity. High-throughput screening identified several natural compounds as nuclear ${\beta}23$ inhibitors, including peucedanocoumarin III (PCIII). Interestingly, PCIII accelerates disaggregation and proteasomal clearance of both nuclear and cytosolic ${\beta}23$ aggregates and protects SH-SY5Y cells from toxicity induced by ${\beta}23$ expression. Of translational relevance, PCIII disassembled fibrils and enhanced clearance of cytosolic and nuclear protein aggregates in cellular models of huntingtin and ${\alpha}$-synuclein aggregation. Moreover, cellular toxicity was diminished with PCIII treatment for polyglutamine (PolyQ)-huntingtin expression and ${\alpha}$-synuclein expression in conjunction with 6-hydroxydopamine (6-OHDA) treatment. Importantly, PCIII not only inhibited ${\alpha}$-synuclein aggregation but also disaggregated preformed ${\alpha}$-synuclein fibrils in vitro. Taken together, our results suggest that a Tet-Off ${\beta}23$ cell model could serve as a robust platform for screening effective lead compounds inhibiting nuclear or cytosolic protein aggregates. Brain-permeable PCIII or its derivatives could be beneficial for eliminating established protein aggregates.