• Archives of Pharmacal Research
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• v.23 no.1
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• pp.35-41
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• 2000

In order to investigate the stereochemical requirements of planar structure at 4-position of 4-phenyl-1-arylsulfonylimidazolidinones (1) for their cytoxicities against human cancer cell lines, the size, the distance from imidazolidinone ring, and the conformation of this moiety were variegated. Replacement of phenyl moiety with naphthyl in compounds 2 and 3 or benzyl moiety in compound 4 sharply reduced activity of 1. Conformational restriction on phenyl ring in compound 5 also resulted in the loss of activity of 1. Therefore, phenyl moiety without any substituents directly attached to imidazolidinone ring of 1 should be considered as an essential pharmacophore for this analog.

• Bulletin of the Korean Chemical Society
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• v.33 no.8
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• pp.2627-2634
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• 2012

Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin derivatives with high activity against resistant pathogens, a series of novel ${\beta}$-methoxyacrylate analogues were designed and synthesized by integrating substituted pyrimidine with a strobilurin pharmacophore. The compounds were confirmed and characterized by infrared, $^1H$ nuclear magnetic resonance, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds (1a-1h) exhibited potent antifungal activities against Colletotrichum orbiculare, Botrytis cinerea Pers and Phytophthora capsici Leonian at the concentration of 50 ${\mu}g/mL$. Exhilaratingly, compound 1d (R=3-trifluoromethylphenyl) showed better antifungal activity against all the tested fungi than the commercial strobilurin fungicide azoxystrobin.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.111-116
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• 2014

Objective: To study potential targets of Danshensu via dual inverse docking. Method: PharmMapper and idTarget servers were used as tools, and the results were checked with the molecular docking program autodock vina in PyRx 0.8. Result: The disease-related target HRas was rated top, with a pharmacophore model matching well the molecular features of Danshensu. In addition, docking results indicated that the complex was also matched in terms of structure, H-bonds, and hydrophobicity. Conclusion: Dual inverse docking indicates that HRas may be a potential anticancer target of Danshensu. This approach can provide useful information for studying pharmacological effects of agents of interest.

• YAKHAK HOEJI
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• v.38 no.6
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• pp.791-794
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• 1994

Sixteen kinds of naturally occurring phenolic compounds including 5 stilbenes, 7 flavonoids and 4 anthraquinones were examined in the inhibitory activity against rat liver AADC(aromatic L-amino acid decarboxylase) in vitro, using 5-hydroxytryptophan as a substrate. Three hydroxystilbenes, resveratrol 1, rhapontigenin 3 and piceatanol 5, which were known to be monoamine oxidase A inhibitors, exhibited a significant inhibition against AADC($IC_{50}$=20, 8 and $5\;{\mu}M$, respectively). By the comparison of the activity of each phenolic compound, it was suggested that the 3',4'-dihydroxyphenyl group of stilbenes or flavones was the best pharmacophore for the AADC inhibitory activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4301-4305
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• 2014

Tanshinone IIA is a pharmacologically active ingredient extracted from Danshen, a Chinese traditional medicine. Its molecular mechanisms are still unclear. The present study utilized computational approaches to uncover the potential targets of this compound. In this research, PharmMapper server was used as the inverse docking tool andnd the results were verified by Autodock vina in PyRx 0.8, and by DRAR-CPI, a server for drug repositioning via the chemical-protein interactome. Results showed that the retinoic acid receptor alpha ($RAR{\alpha}$), a target protein in acute promyelocytic leukemia (APL), was in the top rank, with a pharmacophore model matching well the molecular features of Tanshinone IIA. Moreover, molecular docking and drug repurposing results showed that the complex was also matched in terms of structure and chemical-protein interactions. These results indicated that $RAR{\alpha}$ may be a potential target of Tanshinone IIA for APL. The study can provide useful information for further biological and biochemical research on natural compounds.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.453-468
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• 2016

There is a conserved ATPase domain in topoisomerase II (topo II) and heat shock protein 90 (Hsp90) which belong to the GHKL (gyrase, Hsp90, histidine kinase, and MutL) family. The inhibitors that target each of topo II and Hsp90 are intensively studied as anti-cancer drugs since they play very important roles in cell proliferation and survival. Therefore the development of dual targeting anti-cancer drugs for topo II and Hsp90 is suggested to be a promising area. The topo II and Hsp90 inhibitors, known to bind to their ATP binding site, were searched. All the inhibitors investigated were docked to both topo II and Hsp90. Four candidate compounds as possible dual inhibitors were selected by analyzing the molecular docking study. The pharmacophore model of dual inhibitors for topo II and Hsp90 were generated and the design of novel dual inhibitor was proposed.

• Bulletin of the Korean Chemical Society
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• v.31 no.11
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• pp.3318-3326
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• 2010

Five new series of 3,4-ethylenedioxythiophene derivatives carrying important pharamacophores, viz., amide, ester, ether and active secondary aryl moieties have been designed and synthesized through multistep reactions starting from thiodiglycolic ester and diethyl oxalate. They have been characterized by elemental and spectral data. All the target compounds have been screened for their anticonvulsant activity at three different models viz. maximal electroshock (MES), subcutaneous metrazole (scMET), and 6 Hz screen and evaluated for their neurotoxicity in rotorod model. Compound 6a emerged as lead with no neurotoxicity. All the five series of compounds are safe in the toxicity studies at the maximum dose of 300 mg/kg of body weight. Amongst the tested compounds, the ester pharmacophore with thioamide fragment has showed better activity than the other analogs.

• YAKHAK HOEJI
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• v.49 no.6
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• pp.505-510
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• 2005

Allylthio group of allicin and other organosulfur compounds which are isolated from garlic is considered as a pharmacophore, a key structure component of the molecule which is responsible biological activities. In the foregoing studies various 3-allylthio -6- alkoxypyridazine derivatives (K- compounds ) and 3-allylthio -6- alkylthiopyridazine derivatives(Thio-K-compounds) were synthesized and their biological activities were tested in vivo. They showed good hepatoprotective activities on the carbon tetrachloride-treated mouse and aflatoxin Bl-treated rat and chemopreventive activities on bepatocarcinoma cells in rat as expected. Now 3-allylthio-6-heterocyclylalkylaminopyridazine derivatives that the oxygen atom at 6-Position of 3-allylthio-6-alkoxypyridazine is replaced by nitrogen (N) were synthesiz ed and their activities were tested in vitro against SK-Hep-1 human liver cancer cells. They showed good chemopreventive activities on hepatocarcinoma cells.

• Bulletin of the Korean Chemical Society
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• v.27 no.12
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• pp.1969-1975
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• 2006

3D-QSAR model that correlates the biological activities with the chemical structures of quipazine derivatives acting on the serotonine transporter (SERT) was developed by comparative molecular field analysis (CoMFA). Total 8 models were constructed and a more accurate model, using close 1 $\AA$ grid spacing and StDev*Coefficients weight value gave better results. The contour maps with the best model, the resulting cross-validated correlation ($q^2$ : 0.744), and non-cross-validated correlation ($r^2$ : 0.966) indicate the steric and electrostatic environment of inhibitors in the SERT binding pocket. This study can be used as a putative picture of the pharmacophore in the design of novel and potent inhibitors.

• Bulletin of the Korean Chemical Society
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• v.28 no.2
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• pp.211-219
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• 2007

The subtle but significant differences and thereby the lack of consensus in active site structures among the crystal structures of cyclin-dependent kinase 2 (CDK2) has hampered structure-based drug design. In this study, we devised a simple but effective ‘mutation, pharmacophore-guided docking, followed by mutation' strategy to generate an “average” CDK2 structure, which was used for ligand docking study to successfully reproduce 30 out of 32 X-ray ligand positions within 2.0 A of heavy atom RMSD. This novel docking method was applied for structure-based 3D QSAR with CoMSIA study of a series of structurally related ligands, which showed a good discrimination between CDK2 binders and nonbinders.