• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3119-3121
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• 2012

Non-small-cell lung cancer (NSCLC) is a leading cause of cancer deaths worldwide. Crizotinib has been approved by the U.S. Food and Drug Administration for the treatment of patients with advanced NSCLC. However, understanding of mechanisms of action is still limited. In our studies, we confirmed crizotinib-induced apoptosis in A549 lung cancer cells. In order to assess mechanisms, small molecular docking technology was used as a preliminary simulation of signaling pathways. Interesting, our results of experiments were consistent with the results of computer simulation. This indicates that small molecular docking technology should find wide use for its reliability and convenience.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.65.2-65.2
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• 2003

88 selective COX-2 inhibitors belonging to three chemical classes (triaryl rings, diaryl cycloalkanopyrazoles, and diphenyl hydrazides) were studied using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Partial least squares analysis produced statistically significant models with q values of 0.84 and 0.79 for CoMFA and CoMSIA, respectively. The key spatial properties were detected by careful analysis of the isocontour maps. The binding energies calculated from flexible docking correlated with inhibitory activities by the least-squares fit method. (omitted)

• Bulletin of the Korean Chemical Society
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• v.29 no.7
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• pp.1311-1314
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• 2008

Bacillus halodurans O-methyltransferase (BhOMT) is an S-adenosylmethionine dependent methyltransferase. In our previous study, three dimensional structure of the BhOMT has been determined by comparative homology modeling and automated docking study showed that two hydroxyl groups at 3'- and 4'-position in Bring and structural rigidity of C-ring resulting from the double bond characters between C2 and C3 of flavonoid, were key factors for interaction with BhOMT. In the present study, BhOMT was cloned and expressed. Binding assay was performed on purified BhOMT using fluorescence experiments and binding affinity of luteolin, quercetin, fisetin, and myricetin were measured in the range of $10^7$. Fluorescence quenching experiments indicated that divalent cation plays a critical role on the metal-mediated electrostatic interactions between flavonoid and substrate binding site of BhOMT. Fluorescence study confirmed successfully the data obtained from the docking study and these results imply that hydroxyl group at 7-position of luteolin, quercetin, fisetin, and myricetin forms a stable hydrogen bonding with K211 and carboxyl oxygen of C-ring forms a stable hydrogen bonding with R170. Hydroxyl group at 3'-and 4'-position in the B-ring also has strong $Ca^{2+}$ mediated electrostatic interactions with BhOMT.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.185.1-185.1
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• 2000

• Journal of Integrative Natural Science
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• v.13 no.4
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• pp.170-180
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• 2020

Abnormal regulation, hyperphosphorylation, and aggregation of the tau protein are the hallmark of several types of dementia, including Alzheimer's Disease. Increased activity of Glycogen Synthase Kinase-3β (GSK-3β) in the Central Nervous System (CNS), increased the tau hyperphosphorylation and caused the neurofibrillary tangles (NFTs) formation in the brain cells. Over the last two decades, numerous adenosine triphosphate (ATP) competitive inhibitors have been discovered that show inhibitory activity against GSK-3β. But these compounds exhibited off-target effects which motivated researchers to find new GSK-3β inhibitors. In the present study, we have collected the dataset of 31 C-Glycosylflavones derivatives that showed inhibitory activity against GSK-3β. Among the dataset, the most active compound was docked with the GSK-3β and molecular dynamics (MD) simulation was performed for 50 ns. Based on the 50 ns MD pose of the most active compound, the other dataset compounds were sketched, minimized, and aligned. The 3D-QSAR based Comparative Molecular Field Analysis (CoMFA) model was developed, which showed a reasonable value of q2=0.664 and r2=0.920. The contour maps generated based on the CoMFA model elaborated on the favorable substitutions at the R2 position. This study could assist in the future development of new GSK-3β inhibitors.

• Reproductive and Developmental Biology
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• v.34 no.1
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• pp.7-13
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• 2010

The binding affinity constants ($p(Od)_{50}$) and molecular docking scores (OS) between porcine odorant binding proteins pOBP (1HQP) and pPBP (1GM6) as receptor and a series of tetrahydrofuran-2-yl (A & B) analogues as substrate, and their interactions were discussed quantitatively using three-dimensional quantitative structure-activity relationship (30-QSAR) models. The statistical qualities of the optimized CoMF A models for pOBP were better than those of the CoMSIA models. The binding affinity constants and OS between substrate and receptor molecules were dependent upon steric and hydrophobic interaction. The DS constants of the substrates into the binding site of OBP (1HQP) were bigger than those of PBP (1GM6). The resulting contour maps produced by the optimized CoMFA model were used to identify the structural features relevant to the binding affinity in binding site of pOBP.

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.2065-2071
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• 2014

${\beta}$-Secretase (beta-amyloid converting enzyme 1 [BACE1]) is involved in the first and rate-limiting step of ${\beta}$-amyloid ($A{\beta}$) peptides production, which leads to the pathogenesis of Alzheimer's disease(AD). Therefore, inhibition of BACE1 activity has become an efficient approach for the treatment of AD. Ligand-based and docking-based 3D-quantitative structure-activity relationship (3D-QSAR) studies of acyl guanidine analogues were performed with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to obtain insights for designing novel potent BACE1 inhibitors. We obtained highly reliable and predictive CoMSIA models with a cross-validated $q^2$ value of 0.725 and a predictive coefficient $r{^2}_{pred}$ value of 0.956. CoMSIA contour maps showed the structural requirements for potent activity. 3D-QSAR analysis suggested that an acyl guanidine and an amide group in the $R_6$ substituent would be important moieties for potent activity. Moreover, the introduction of small hydrophobic groups in the phenyl ring and hydrogen bond donor groups in 3,5-dichlorophenyl ring could increase biological activity.

• Journal of Integrative Natural Science
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• v.9 no.4
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• pp.268-274
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• 2016

Filariasis causing nematode Brugia malayi is shown to harbor wolbachia bacteria as symbionts. The sequenced genome of the wolbachia endosymbiont from B.malayi (wBm) offers an unprecedented opportunity to identify new wolbachia drug targets. Hence the enzyme carbonic anhydrase from wolbachia endosymbiont of Brugia malayi (wBm) which is responsible for the reversible interconversion of carbon dioxide and water to bicarbonate and protons (or vice versa) is chosen as the drug target for filariasis. This enzyme is thought to play critical functions in bacteria by involving in various steps of their life cycle which are important for survival, The 3D structure of wBm carbonic anhydrase is predicted by selecting a suitable template using the similarity search tool, BLAST. The BLAST results shows a hexapeptide transferase family protein from Anaplasma phagocytophilum (PDB ID: 3IXC) having 77% similarity and 54% identity with wBm carbonic anhydrase. Hence the above enzyme is chosen as the template and the 3D structure of carbonic anhydrase is predicted by the tool Modeller9v7. Since the three dimensional structure of carbonic anhydrase from wolbachia endosymbiont of Brugia malayi has not yet solved, attempts were made to predict this protein. The predicted structure is validated and also molecular docking studies are carried out with the suitable inhibitors that have been solved experimentally.

• Journal of Microbiology and Biotechnology
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• v.22 no.7
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• pp.917-922
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• 2012

Homology modeling of Streptomyces peucetius CYP147F1 was constructed using three cytochrome P450 structures, CYP107L1, CYPVdh, and CYPeryF, as templates. The lowest energy SPCYP147F1 model was then assessed for stereochemical quality and side-chain environment by Accelrys Discovery Studio 3.1 software. Further activesite optimization of the SPCYP147F1 was performed by molecular dynamics to generate the final SPCYP147F1 model. The substrate limonene was then docked into the model. The model-limonene complex was used to validate the active-site architecture, and functionally important residues within the substrate recognition site were identified by subsequent characterization of the secondary structure. The docking of limonene suggested that SPCYP147F1 would have broad specificity with the ligand based on the two different orientations of limonene within the active site facing to the heme. Limonene with C7 facing the heme with distance of $3.4{\AA}$ from the Fe was predominant.

• Journal of the Korean Chemical Society
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• v.66 no.3
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• pp.194-201
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• 2022

A simple, efficient, and cost-effective method has been employed for the synthesis of 2,4,5-trisubstituted imidazole derivatives (3a-j) containing quinoline substituent at 2^nd position. Title compounds were obtained by multicomponent reaction (MCR), involving aryl substituted 1,2-diketone, quinoline carbaldehyde and ammonium acetate in the presence of acetic acid solvent under mild reaction conditions. The newly synthesized quinoline containing imidazole derivatives were confirmed through FT-IR, ¹H-NMR, ¹³C-NMR and mass spectral analysis. In-vitro microplate alamar blue assay (MABA) to determine the MIC (minimum inhibitory concentration) values against Mycobacterium tuberculosis H37Rv was performed for the synthesized compounds. The synthesized compounds exhibited activity against Mycobacterium tuberculosis and among which compounds, 3d, 3f and 3i showed good activity. The highest activity was showed with compound 3i. The anti-mycobacterial activity results are well correlated with the computational molecular docking analysis, which was performed for the synthesized compounds prior to the evaluation of the activity.