• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.108-115
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• 2023

Numerous psychotropic and addictive substances possess structural features similar to those of β-phenethylamine (β-PEA). In this study, we selected 29 β-PEA derivatives and determined their structure-activity relationship (SAR) to their ability to inhibit dopamine (DA) reuptake; conducted docking simulation for two selected compounds; and identified their potential functionals. The compounds were subdivided into arylethylamines, 2-(alkyl amino)-1-arylalkan-1-one derivatives and alkyl 2-phenyl-2-(piperidin-2-yl)acetate derivatives. An aromatic group, alkyl group, and alkylamine derivative were attached to the arylethylamine and 2-(alkyl amino)-1-arylalkan-1-one derivatives. The inhibitory effect of the compounds on dopamine reuptake increased in the order of the compounds substituted with phenyl, thiophenyl, and substituted phenyl groups in the aromatic position; compounds with longer alkyl groups and smaller ring-sized compounds at the alkylamine position showed stronger inhibitory activities. Docking simulation conducted for two compounds, 9 and 28, showed that the (S)-form of compound 9 was more stable than the (R)-form, with a good fit into the binding site covered by helices 1, 3, and 6 of human dopamine transporter (hDAT). In contrast, the (R, S)-configuration of compound 28 was more stable than that of other isomers and was firmly placed in the binding pocket of DAT bound to DA. DA-induced endocytosis of dopamine D₂ receptors was inhibited when they were co-expressed with DAT, which lowered extracellular DA levels, and uninhibited when they were pretreated with compound 9 or 28. In summary, this study revealed critical structural features responsible for the inhibition of DA reuptake and the functional role of DA reuptake inhibitors in regulating D₂ receptor function.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.176-182
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• 2023

Among 14 subtypes of serotonin receptors (5-HTRs), 5-HT_2AR plays important roles in drug addiction and various psychiatric disorders. Agonists for 5-HT_2AR have been classified into three structural groups: phenethylamines, tryptamines, and ergolines. In this study, the structure-activity relationship (SAR) of phenethylamine and tryptamine derivatives for binding 5-HT_2AR was determined. In addition, functional and regulatory evaluation of selected compounds was conducted for extracellular signal-regulated kinases (ERKs) and receptor endocytosis. SAR studies showed that phenethylamines possessed higher affinity to 5-HT_2AR than tryptamines. In phenethylamines, two phenyl groups were attached to the carbon and nitrogen (R³ ) atoms of ethylamine, the backbone of phenethylamines. Alkyl or halogen groups on the phenyl ring attached to the β carbon exerted positive effects on the binding affinity when they were at para positions. Oxygen-containing groups attached to R³ exerted mixed influences depending on the position of their attachment. In tryptamine derivatives, tryptamine group was attached to the β carbon of ethylamine, and ally groups were attached to the nitrogen atom. Oxygen-containing substituents on large ring and alkyl substituents on the small ring of tryptamine groups exerted positive and negative influence on the affinity for 5-HT_2AR, respectively. Ally groups attached to the nitrogen atom of ethylamine exerted negative influences. Functional and regulatory activities of the tested compounds correlated with their affinity for 5-HT_2AR, suggesting their agonistic nature. In conclusion, this study provides information for designing novel ligands for 5-HT_2AR, which can be used to control psychiatric disorders and drug abuse.

• International Journal of Quality Innovation
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• v.6 no.2
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• pp.17-30
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• 2005

The Internet can provide benefits obtained from changing the structure of a business, such as emphasizing the importance of different types of personnel. In addition, the Internet alters the process for business activity, both within and outside the organization. Using structural equation modeling, I empirically test a number of hypothesized relationship based on a sample of 126 Internet Community users. The results are as follows: loyalty is significantly influenced by trust and relationship, repeat purchase is significantly influenced bye-loyalty. In addition, word of mouth is significantly influenced by e-loyalty.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.1-10
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• 2020

FK506, also known as tacrolimus, is a clinically important immunosuppressant drug and has promising therapeutic potentials owing to its antifungal, neuroprotective, and neuroregenerative activities. To generate various FK506 derivatives, the structure of FK506 has been modified by chemical methods or biosynthetic pathway engineering. Herein, we describe the mode of the antifungal action of FK506 and the structure-activity relationship of FK506 derivatives in the context of immunosuppressive and antifungal activities. In addition, we discuss the neurotrophic mechanism of FK506 known to date, along with the neurotrophic FK506 derivatives with significantly reduced immunosuppressive activity. This review suggests the possibility to generate novel FK506 derivatives as antifungal as well as neuroregenerative/neuroprotective agents.

• Journal of the Korean Chemical Society
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• v.59 no.6
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• pp.483-487
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• 2015

The different calculated quantum chemical descriptors by DFT method were used for prediction of some sulphanilamide Schiff bases inhibitor activity as a binding constant (log K). Multiple linear regression (MLR) and artificial neural network (ANN) were employed for developing the useful quantitative structure activity relationship (QSAR) model. The obtained results presented superiority of ANN model over the MLR one. The offering QSAR model is very easy to computation and Physico-Chemically interpretable. Sensitivity analysis was used to determine the relative importance of each descriptor in ANN model. The order of importance of each descriptor according to this analysis is: molecular volume, molecular weight and dipole moment, respectively. These descriptors appear good information related to different structure of sulphanilamide Schiff bases can participate in their inhibitor activity.

• YAKHAK HOEJI
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• v.46 no.6
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• pp.375-380
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• 2002

In this study, newly designed COX-2 inhibitors, synthetic derivatives of benzothiazine-3-carboxamide, were screened in vitro for selectivity of COX-1 and COX-2 inhibition properties. 7-Bromo-1,2-benzoisothiazine derivatives were obtained from 4-bromotoluene over the chlorosulfonation, amination and oxidation. And benzothiazine ring was synthesized through Gabriel-Colmann rearrangement reaction. To evaluate inhibitory effect of COX-2, synthetic derivatives of benzothiazine-3-carboxamide were tested with accumulation of prostaglandin by lipopolysaccharide in aspirin-treated murine macropharge cell. Some of the synthesized lead compounds have potentially shown the structure-activity relationship for selectivity of COX-2 inhibition activity.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.187.3-188
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• 2003

Structure-activity relationship studies of allylamine type of antimycotics were carried out to evaluate the effect of naphthyl and methyl portion of naftifine. Compounds with 4-fluorphenyl, 2-fluorophenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl, 4-nitrophenyl, and 2,3-dihydro-benzo[l,4]dioxin-6-yl instead of naphthyl group with hydrogen, methyl, and ethyl in the place of methyl in naftifine were synthesized and tested their in vitro anti-fungal activity against five different fungi. Eight compounds showed significant antifungal activity against T. mentagrophytes. (omitted)

• The Korean Journal of Pesticide Science
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• v.6 no.4
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• pp.231-243
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• 2002

Starting with linear free energy relationships (LFER), drug design to mimic of the activated complexes at transition state, and hydrolysis mechanisms to control the potency and residual properties of pesticides were introduced and summarized for the necessity. In order to understand the searching or development of new agrochemicals by two dimensional quantitative structure-activity relationship (2D QSAR) methodology, a series of the various descriptors, steric constants, electronic constants including quantum pharmacological parameters and hydrophobic constants were classified and discussed for results of the several studied cases. In addition, the processes of development of new agrochemicals by QSAR techniques were introduced simply.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.937-943
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• 2004

Recent investigations have shown that certain flavonoids, especially flavone derivatives, inhibit nitric oxide (NO) production by inducible NO synthase (iNOS) in macrophages, which contrib-ute their anti-inflammatory action. For the purpose of finding the optimized chemical structures of flavonoids that inhibit NO production, various A- and B-ring substituted flavones were syn-thesized and evaluated for their inhibitory activity using lipopolysaccharide-treated RAW 264.7 cells. It was found that the optimal chemical structures were A-ring 5,7-dihydroxyflavones hav-ing the B-ring 2＇,3＇-dihydroxy or 3＇,4＇-dihydroxy or 3＇,4＇-hydroxy/methoxy (methoxy/hydroxy) groups. These structurally optimized compounds were revealed to be down-regulators of iNOS induction, but not direct iNOS inhibitors. Of these derivatives that were evaluated, 2＇,3＇,5,7-tet-rahydroxyflavone and 3＇,4＇,5,7-tetrahydroxyflavone (Iuteolin) showed the strongest inhibition. The $IC_{50}$/ values for these compounds were 19.7 and 17.1 11M, respectively. Therefore, these compounds may have a potential as new anti-inflammatory agents.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.270-274
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• 2002

Chromatographic separation of the stem bark extract of Mitragyna stipulosa afforded triterpene derivatives ursolic acid (1), quinovic acid (2), quinivic acid $3-O-{\beta}-D-glucopyranoside$ (3, quinovin glycoside C), quinovic acid 3-O-[$(2-O-sulfo)-{\beta}-D-quinovopyranoside$] (4, zygophyloside D) and quinovic acid $3-O-{\beta}-D-quinovopyranosyl-27-O-{\beta}-D-glucopyranosyl$ ester (5, zygophyloside B). These five compounds were subjected to the cytotoxicity on MTT assay system. Compound 1 among tested showed the most potent cytotoxicity. Quinovic acid showed less potent cytotoxicity than ursolic acid and sugar linkages to 2 decreased the cytotoxicity. Compound 4 more potent than 3 with indicate that the sulfonyl group significantly enhances the activity. This indicates that the glycosidic linkage in ursane-type triterpenoids has mainly negative effect on cytotoxicity unlike in oleanane-type glycosides.