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1.
Braz. j. med. biol. res ; 52(3): e8281, 2019. tab, graf
Article in English | LILACS | ID: biblio-989461

ABSTRACT

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (lo) and liquid-disordered (ld) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of lo phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.


Subject(s)
Phenylpropionates/chemistry , Lipid Bilayers/chemistry , Liposomes/chemistry , Reference Values , Temperature , Time Factors , Calorimetry, Differential Scanning , Cholesterol/chemistry , Reproducibility of Results , Microscopy, Confocal , Scattering, Small Angle , Laurates , Microscopy, Fluorescence , Models, Chemical , 2-Naphthylamine/analogs & derivatives
2.
An. acad. bras. ciênc ; 90(1): 541-555, Mar. 2018. tab, graf
Article in English | LILACS | ID: biblio-886922

ABSTRACT

ABSTRACT Vinasse is a byproduct of the process of distillation of sugarcane juice for the manufacture of sugar and alcohol. Because it is rich in nutrients, mainly potassium (K), is used as fertilizer and applied via fertigation, without concerning for the fate of this compound in the soil. Thus, the objective of the study was to evaluate the interactions of the potassium ion (K+), applied via vinasse in a soil representative of the sugarcane zone of the State of Pernambuco using adsorption isotherms. The methodology was based on physical, chemical and soil mineralogical characterization, as well as equilibrium batch tests, where the experimental curves were fitted by Langmuir and Freundlich isotherm models. The results allowed to infer that the Freundlich model showed better fit of the curve in both forms: linear and non-linear (direct fit); the non-linear model was selected due to the values ​​of coefficient of determination (R²). The interaction between potassium and soil occurred mainly with organic matter and the presence of soil kaolinite, because they showed negative ions on the external surface, thereby promoting potassium adsorption. Soil potassium adsorption capacity was higher for the first layer (0-20 cm) and decreased along the depth profile.


Subject(s)
Potassium/chemistry , Soil/chemistry , Reference Values , Linear Models , Adsorption , Saccharum/chemistry , Fertilizers , Ions , Models, Chemical
3.
Article in Chinese | WPRIM | ID: wpr-771530

ABSTRACT

In this study, bioinformatics methods such as molecular docking and network pharmacology were adopted to establish Xiaoxuming Decoction (XXMD) "compound-vasodilatory and vasoconstrictory related G protein-coupled receptors (GPCR) targets" network, then the vascular function regulatory effective components and the potential targets of XXMD were analyzed. Based on the XXMD herb sources, the chemical structures of the compounds were retrieved from the national scientific data sharing platform for population and health pharmaceutical information center, TCMSP database and the latest research literatures. The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties. Then, five kinds of vasodilatory and vasoconstrictory related GPCR crystal structure including 5-HT receptors (5-HT1AR, 5-HT1BR), AT1R, β2-AR, hUTR and ETB were retrieved from RCSB Protein Data Bank database or constructed by homology modeling of Discovery Studio 4.1 built-in modeling tools. After virtual screening by Libdock molecular docking, the highest rated 50 compounds of each target were collected and analyzed. The collected data were further used to construct and analyze the network by Cytoscape 3.4.0. The results showed that most of the chemical composition effects were associated with different vasodilatory and vasoconstrictory related GPCR targets, while a few effective components could be applied to multiple GPCR targets at the same time, therefore forming synergies and vasorelaxant effects of XXMD.


Subject(s)
Databases, Protein , Drugs, Chinese Herbal , Models, Chemical , Molecular Docking Simulation , Receptors, G-Protein-Coupled , Metabolism , Vasodilation
4.
Pakistan Journal of Pharmaceutical Sciences. 2017; 30 (1): 179-186
in English | IMEMR | ID: emr-185756

ABSTRACT

The objective of this study was to assess the quality of six different brands of enteric coated Ketoprofen 100 mg tablets, KPB[2] to KPB[6] are available in commercial market of Karachi, Pakistan, while KPB[1] was obtained from international source. We performed different physico-chemical assessments i.e. weight variation, diameter, hardness, friability, thickness, disintegration, content uniformity, assay and dissolution test. Results of all the investigations were found to be in adequate limits. Also pharmaceutical equivalence was determined by selecting different tests and assay assessment. Furthermore, in vitro therapeutic equivalence was also estimated at phosphate buffer pH 6.8 and 7.5. Results were evaluated by one way ANOVA, model independent and model dependent methods. ANOVA results showed that release behaviour were found to be similar as p values >0.05, also KPB[1] - KPB[6] followed Weibull model at different dissolution media. Results indicated that innovator and brands not only passes the pharmaceutical equivalence assessment but also comply with the in vitro therapeutic equivalence


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/standards , Tablets, Enteric-Coated , Drug Compounding , Quality Control , Models, Chemical , Pakistan
5.
Article in English | WPRIM | ID: wpr-170672

ABSTRACT

OBJECTIVES: This study aimed to analyze the mineral composition of naturally- and artificially-produced caries-affected root dentin and to determine the elemental incorporation of resin-modified glass ionomer (RMGI) into the demineralized dentin. MATERIALS AND METHODS: Box-formed cavities were prepared on buccal and lingual root surfaces of sound human premolars (n = 15). One cavity was exposed to a microbial caries model using a strain of Streptococcus mutans. The other cavity was subjected to a chemical model under pH cycling. Premolars and molars with root surface caries were used as a natural caries model (n = 15). Outer caries lesion was removed using a carbide bur and a hand excavator under a dyeing technique and restored with RMGI (FujiII LC, GC Corp.). The weight percentages of calcium (Ca), phosphate (P), and strontium (Sr) and the widths of demineralized dentin were determined by electron probe microanalysis and compared among the groups using ANOVA and Tukey test (p < 0.05). RESULTS: There was a pattern of demineralization in all models, as visualized with scanning electron microscopy. Artificial models induced greater losses of Ca and P and larger widths of demineralized dentin than did a natural caries model (p < 0.05). Sr was diffused into the demineralized dentin layer from RMGI. CONCLUSIONS: Both microbial and chemical caries models produced similar patterns of mineral composition on the caries-affected dentin. However, the artificial lesions had a relatively larger extent of demineralization than did the natural lesions. RMGI was incorporated into the superficial layer of the caries-affected dentin.


Subject(s)
Bicuspid , Calcium , Dentin , Electron Probe Microanalysis , Glass , Hand , Humans , Hydrogen-Ion Concentration , Microscopy, Electron, Scanning , Miners , Models, Chemical , Molar , Root Caries , Streptococcus mutans , Strontium
6.
Article in English | WPRIM | ID: wpr-728445

ABSTRACT

Caffeic acid phenethyl ester (CAPE), derived from honeybee hives, is a bioactive compound with strong antioxidant activity. This study was designed to test the neuroprotective effect of CAPE in 3-nitropropionic acid (3NP)-induced striatal neurotoxicity, a chemical model of Huntington's disease (HD). Initially, to test CAPE's antioxidant activity, a 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) antioxidant assay was employed, and CAPE showed a strong direct radical-scavenging eff ect. In addition, CAPE provided protection from 3NP-induced neuronal cell death in cultured striatal neurons. Based on these observations, the in vivo therapeutic potential of CAPE in 3NP-induced HD was tested. For this purpose, male C57BL/6 mice were repeatedly given 3NP to induce HD-like pathogenesis, and 30 mg/kg of CAPE or vehicle (5% dimethyl sulfoxide and 95% peanut oil) was administered daily. CAPE did not cause changes in body weight, but it reduced mortality by 29%. In addition, compared to the vehicle-treated group, robustly reduced striatal damage was observed in the CAPE-treated animals, and the 3NP-induced behavioral defi cits on the rotarod test were signifi cantly rescued after the CAPE treatment. Furthermore, immunohistochemical data showed that immunoreactivity to glial fibrillary acidic protein (GFAP) and CD45, markers for astrocyte and microglia activation, respectively, were strikingly reduced. Combined, these data unequivocally indicate that CAPE has a strong antioxidant eff ect and can be used as a potential therapeutic agent against HD.


Subject(s)
Animals , Astrocytes , Body Weight , Cell Death , Dimethyl Sulfoxide , Glial Fibrillary Acidic Protein , Humans , Huntington Disease , Male , Mice , Microglia , Models, Chemical , Mortality , Neurons , Neuroprotective Agents , Rotarod Performance Test , Urticaria
7.
Electron. j. biotechnol ; 18(2): 68-76, Mar. 2015. ilus, graf, tab
Article in English | LILACS | ID: lil-745572

ABSTRACT

Background Industrial food processing induces protein glycation modifications and toxic advanced glycation end products (AGEs) which affect human health. Therefore, it is of interest to monitor AGEs in food processing. The present study was carried out to investigate the influence of lotus seedpod oligomeric procyanidin (LSOPC) concentrations, solution pH value and metal ions on AGE formation by heat treatment of lactose-lysine model solutions. Ne-(carboxymethyl) lysine (CML), as one of the common AGEs was also determined by HPLC-MS/MS in this experiment. Results The results showed that LSOPC can inhibit the formation of AGEs effectively at higher concentrations, lower temperature, and it can reverse the promotion function of metal ions because of its high inhibition activity. Also, LSOPC can inhibit CML formation in the Maillard reaction as well. Conclusion These results indicated that LSOPC could be used as functional food ingredients to inhibit AGE formation.


Subject(s)
Seeds/chemistry , Glycation End Products, Advanced/metabolism , Proanthocyanidins/metabolism , Temperature , Maillard Reaction , Chromatography, High Pressure Liquid , Lotus/chemistry , Hydrogen-Ion Concentration , Lactose/chemistry , Lysine/chemistry , Models, Chemical
8.
Mem. Inst. Oswaldo Cruz ; 110(1): 142-144, 03/02/2015. tab, graf
Article in English | LILACS | ID: lil-741622

ABSTRACT

Monitoring phlebotomine sandflies in urban areas is key for epidemiological studies in susceptible populations. This paper describes sandfly fauna that were present in an urban area of the municipality of Tapachula, Chiapas, Mexico, and were captured with Shannon and CDC light traps. During February and March of 2014, 1,442 sandflies were captured, specifically Lutzomyia cruciata (Coquillet) (98.8%), Lutzomyia cayennensis cayennensis (Floch and Abonnenc) (0.8%), Lutzomyia chiapanensis (Dampf) (0.3%) and Lutzomyia atulapai (De León) (0.1%). Lu. cruciata was the most abundant and the most frequently trapped species. This is the first record of its remarkable ability to adapt to urban green areas. The three other species trapped represent new records of geographic distribution for the study region. These results indicate the need to establish measures for reducing both human contact with this vector and the risk of possible sites of infection.


Subject(s)
Antioxidants/isolation & purification , Caesalpinia/chemistry , Food Preservatives/isolation & purification , Fruit/chemistry , Models, Chemical , Plant Extracts/isolation & purification , Antioxidants/analysis , Antioxidants/chemistry , Emulsions , Ethanol/chemistry , Food Storage , Flavonoids/analysis , Flavonoids/chemistry , Flavonoids/isolation & purification , Food Preservatives/analysis , Food Preservatives/chemistry , Gallic Acid/analysis , Gallic Acid/chemistry , Gallic Acid/isolation & purification , Hydrogen-Ion Concentration , Oxidation-Reduction , Peru , Principal Component Analysis , Phenols/analysis , Phenols/chemistry , Phenols/isolation & purification , Plant Extracts/chemistry , Spain , Solvents/chemistry , Ultrasonics/methods , Water/chemistry
9.
Article in Korean | WPRIM | ID: wpr-217693

ABSTRACT

The osteoarthritis is being emphasized in South Korea becoming an aged society. It is desirable to use a model that reflects human disease when using an animal model to understand the pathophysiology of osteoarthritis and verify the effective treatment materials. Because naturally occuring osteoarthritis is rare in rodent models, chemical or surgical methods are used to induce diseases. While these methods have the advantages of consistent occurrence and rapid progress of osteoarthritis, it is controversial about whether experimentally-induced osteoarthritis progresses in the same pathophysiology of human disease. The model using injection of chemical materials such as collagenase or monoiodoaceatate in joint space has been widely used. Each method leads to joint damage by chemical joint instability with destruction of articular connective tissue and cartilage cell apoptosis with inhibition of cell metabolism. Anterior cruciate ligament resection model, meniscus resection model, collateral ligament resection model, menisco-tibia ligament resection model and etc. are used as surgical models. These days, it tends to be used menisco-tibia ligament resection model more. It is required to observe the joint damage as well as induction of pain, recently. This review considers how to induce osteoarthritis of knee model used widely, usage of the pathogenesis studies, advantages and disadvantages.


Subject(s)
Animals , Anterior Cruciate Ligament , Apoptosis , Cartilage , Cartilage, Articular , Collagenases , Collateral Ligaments , Connective Tissue , Humans , Joint Instability , Joints , Korea , Ligaments , Metabolism , Models, Anatomic , Models, Animal , Models, Chemical , Osteoarthritis , Osteoarthritis, Knee , Rodentia
10.
Acta Pharmaceutica Sinica ; (12): 1161-1166, 2015.
Article in Chinese | WPRIM | ID: wpr-257012

ABSTRACT

The molecular descriptors of impurities with known structure in cefdinir were calculated, selected and associated with the chromatographic retention behavior to establish a model. This quantitative structure retention relationships (QSRR) model for the related substances of cefdinir was established under specific chromatographic condition and verified by other impurities. 12 molecular descriptors were used to establish the QSRR model, F_AFRBWF, Blbn_J, SsCH3, SssCH2, SsNH2, SssNH, SssS, SHdCH2, EEM_AFc, EEM_AFpl, EEM_XFpl and Pi_MaxQ. The relativity between true values and predictions in QSRR of cefdinir is R2 = 0.9836 (n = 18), ΔRRT is no more than 0.154, as 10.17% in RRT. The results indicate that the QSRR model for the related substances of cefdinir can be used to evaluate the analysis methods for related substances and predict the chromatographic behavior of new impurities, which will provide a new way for the evaluation of the effectiveness for drug quality control.


Subject(s)
Cephalosporins , Chemistry , Reference Standards , Chromatography , Models, Chemical , Quality Control , Structure-Activity Relationship
11.
Indian J Biochem Biophys ; 2014 Oct; 51(5): 350-357
Article in English | IMSEAR | ID: sea-154263

ABSTRACT

The non-proteinogenic amino acids — phenylglycine (PG) and hydroxyphenylglycine (HPG) are crucial components of certain peptidic natural products and are important for the preparation of various medicines. In this, study, the conformation of model dipeptides Ac-X-NHMe of PG, p-HPG and 3, 5-di-hydroxyphenylglycine (3, 5-DHPG) was studied both in R and S form by quantum mechanical (QM) and molecular dynamics approaches. On the energy scale, the conformational states of these molecules in both the R and S were found to be degenerate by QM studies, stabilized by non-covalent interactions like carbonyl--carbonyl interactions, carbonyl-lp··π (aromatic ring) interactions etc. These interactions disappeared/weakened due to interaction of water molecules with carbonyl groups of backbone in simulation and water was found to interact with the aromatic ring through Ow-H··π or Owlp··π interactions. The degeneracy of conformational states was lifted in favor of R-form of PG and DHPG and water molecules interactions with aromatic ring led to non-planarity of the aromatic ring. In simulation studies, irrespective of the starting geometry, the , values for the R form correspond to inverse b/inverse collagen region and for the S-form, the , values correspond to b/collagen region i.e., adopt single conformation. The obtained results were in conformity with the CD spectroscopic data on D-PG and D-p-HPG. The conformational behavior of the unusual amino acids might be of great help in designing of bioactive peptides/peptide based drugs to be realized in single conformation – an essential requirement.


Subject(s)
Benzene/chemistry , Computer Simulation , Glycine/analogs & derivatives , Glycine/chemistry , Models, Chemical , Molecular Conformation , Molecular Dynamics Simulation , Quantum Theory
12.
Indian J Biochem Biophys ; 2014 Oct; 51(5): 343-349
Article in English | IMSEAR | ID: sea-154262

ABSTRACT

Previous studies have shown that COP1 (constitutive photomorphogenic 1) protein of Arabidopsis thaliana plays a crucial role in different aspects of photomorphogenesis. Interaction of COP1 with SPA1 (suppressor of phytochrome A) and other regulatory proteins actively affect light regulatory gene expression in diverse directions. Though several studies have explained the function of COP1 protein, method of its interaction with SPA1 and cryptochromes are still not explained in detail. In this study, in silico analysis was followed to predict the tertiary structure, active site residues, functionally important regions and regular expressions of COP1 protein. Its ease of its interaction with SPA1 and seven other regulatory proteins, namely bZIP transcription factor 56 (HY5), transcription factor HY5-like (HYH), serine/threonine-protein phosphatase 7 (AtPP7), protein long hypocotyl in FAR-RED 1 (HFR1), OBP3-responsive protein 1 (OBP3), transcription factor MYC2 (MYC2/ZBF1) and Z-box binding factor 2 protein (GBF1/ZBF2) was measured using protein-protein docking. Interaction with MYC2 was found to be stronger than with others with a global energy value of -22.46. It was also found that COP1 shared three regions of regular expression with SPA1, the last expression also being present in MYC2/ZBF1 and OBP3. Taken together, the insight into structural and functional properties of COP1 protein presented in this study would be helpful in determining the role of COP1 in unknown mechanisms of photomorphogenesis.


Subject(s)
Amino Acid Sequence , Arabidopsis Proteins/chemistry , Arabidopsis Proteins/ultrastructure , Binding Sites , Computer Simulation , Enzyme Activation , Models, Chemical , Molecular Docking Simulation/methods , Molecular Sequence Data , Protein Binding , Protein Conformation , Protein Interaction Mapping/methods , Structure-Activity Relationship , Substrate Specificity , Ubiquitin-Protein Ligases/chemistry , Ubiquitin-Protein Ligases/ultrastructure
13.
Indian J Biochem Biophys ; 2014 Oct; 51(5): 335-342
Article in English | IMSEAR | ID: sea-154261

ABSTRACT

Perception of molecular mechanism would provide potent additional knowledge on mammalian membrane proteins involved in causing diseases. In human, syntaxin-3 (STX3) is a significant apical targeting protein in the epithelial membrane and in exocytosis process; it also acts as a vesicle transporter by cellular receptor in neutrophils, which is crucial for protein trafficking event. Structurally, syntaxin-3 has hydrophobic domain at carboxyl terminus that directs itself to intra-cellular compartments. In addition, the experimental structure of STX3 is not available and no mutational study has been carried out with natural variants of proteins. Moreover, there is no evidence so far for the natural variant Val286 of STX3 causing any diseases. Hence, in the present study, analyses of residue-based properties of the homology model STX3 were carried out along with mutations at carboxyl terminus of STX3 by implementing protein engineering and in silico approaches. The model structure of STX3 was constructed adopting Modeller v9.11 and the aggregation propensity was analyzed with BioLuminate tool. The results showed that there was reduction in aggregation propensity with point mutation at Val286, instead of Ile, resulting into increasing the structural stability of STX3. In conclusion, the Ccap exposed residue would be a suitable position for further mutational studies, particularly with Val286 of STX3 in human. This approach could gainfully be applied to STX3 for efficient drug designing which would be a valuable target in the cancer treatment.


Subject(s)
Computer Simulation , Humans , Models, Chemical , Models, Molecular , Multiprotein Complexes/chemistry , Multiprotein Complexes/genetics , Multiprotein Complexes/ultrastructure , Mutagenesis, Site-Directed , Mutation/genetics , Protein Binding , Protein Conformation , Protein Folding , Protein Multimerization , Qa-SNARE Proteins/chemistry , Qa-SNARE Proteins/genetics , Qa-SNARE Proteins/ultrastructure , Sequence Homology, Amino Acid
14.
Salud pública Méx ; 56(4): 333-347, jul.-ago. 2014. ilus, tab
Article in Spanish | LILACS | ID: lil-733312

ABSTRACT

Objetivo. Corregir la mala clasificación y mejorar la calidad de la información sobre la mortalidad materna en México. Material y métodos. A través de los registros clínicos y autopsias verbales, se estudiaron todas las defunciones certificadas como maternas y una selección de defunciones de mujeres en edad fértil, cuyas causas fueron consideradas como sospechosas de encubrir una muerte materna; todas ocurridas durante 2011 en México. Resultados. La búsqueda intencionada y reclasificación de muertes maternas permitió rescatar más de 100 muertes que no habían sido registradas ni codificadas inicialmente como maternas y se ratificaron o rectificaron las causas anotadas en los certificados de defunción. Este procedimiento también permitió reclasificar como muertes maternas 297 defunciones de la base preliminar del Instituto Nacional de Estadística y Geografía. Conclusiones. La Búsqueda Intencionada y Reclasificación de Muertes Maternas es un procedimiento muy útil para mejorar la calidad de la información sobre la mortalidad materna.


Objective. To correct the misclassification and improve the quality of information on maternal mortality in Mexico. Materials and methods. Using clinical records and verbal autopsies, we studied all deaths certified as maternal deaths as well as a selection of deaths of women of childbearing age whose causes were considered as suspected of hiding a maternal death, all of which occurred during 2011 within Mexico. Results. The deliberate search of maternal deaths and reclassification allowed the rescue of just over 100 deaths that were not originally registered or coded as maternal and confirmed or corrected the causes of death recorded on death certificates as confirmed maternal deaths. This procedure also allowed the reclassification of 297 maternal deaths of women in the groundwork of the National Institute of Statistics and Geography. Conclusions. International Search and Reclassification of Maternal Deaths is a very useful procedure for improving the classification of cases that were not classified as maternal deaths and the effect was greater with the coding of indirect obstetric deaths.


Subject(s)
Chlorophenols/metabolism , Euryarchaeota/metabolism , Pentachlorophenol/metabolism , Anaerobiosis , Alkanesulfonates/metabolism , Biodegradation, Environmental , Bacteria, Anaerobic/metabolism , Chlorides/metabolism , Models, Chemical , Molybdenum
15.
Article in Chinese | WPRIM | ID: wpr-300214

ABSTRACT

To investigate formation mechanism of secologanic acid sulfonates in sulfur-fumigated buds of Lonicera japonica, secologanic acid was enriched and purified from the sun-dried buds of L. japonica by various column chromatography on macroporus resin HPD-100, silica gel and ODS. The stimulation experiments of sulfur-fumigation process were carried out using secologanic acid reacted with SO2 in the aqueous solution. The reaction mechanism could be involved in the esterification or addition reaction. The present investigation provides substantial evidences for interpreting formation pathway of secologanic acid sulfonates in sulfur-fumigated buds of L. japonica.


Subject(s)
Alkanesulfonates , Chemistry , Carboxylic Acids , Chemistry , Chromatography, High Pressure Liquid , Flowers , Chemistry , Lonicera , Chemistry , Models, Chemical , Molecular Structure , Sulfur , Chemistry , Pharmacology , Sulfur Dioxide , Chemistry , Water , Chemistry
16.
Article in Chinese | WPRIM | ID: wpr-249418

ABSTRACT

<p><b>OBJECTIVE</b>Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptor γt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity.</p><p><b>METHOD</b>Using molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay.</p><p><b>RESULT</b>Molecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt; bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner.</p><p><b>CONCLUSION</b>Dhd can selectively suppress RORγt transcriptional activity.</p>


Subject(s)
Digoxin , Pharmacology , Humans , Models, Chemical , Molecular Docking Simulation , Nuclear Receptor Subfamily 1, Group F, Member 1 , Genetics , Transcription, Genetic
17.
Acta Pharmaceutica Sinica ; (12): 406-410, 2014.
Article in Chinese | WPRIM | ID: wpr-245069

ABSTRACT

In this paper, microcrystalline cellulose WJ101 was used as a model material to investigate the effect of various process parameters on granule yield and friability after dry granulation with a single factor and the effect of comprehensive inspection process parameters on the effect of granule yield and friability, then the correlation between process parameters and granule quality was established. The regress equation was established between process parameters and granule yield and friability by multiple regression analysis, the affecting the order of the size of the order of the process parameters on granule yield and friability was: rollers speed > rollers pressure > speed of horizontal feed. Granule yield was positively correlated with pressure and speed of horizontal feed and negatively correlated rollers speed, while friability was on the contrary. By comparison, fitted value and real value, fitted and real value are basically the same of no significant differences (P > 0.05) and with high precision and reliability.


Subject(s)
Cellulose , Chemistry , Drug Compounding , Methods , Hardness , Models, Chemical , Particle Size , Regression Analysis , Technology, Pharmaceutical , Methods
18.
Acta Pharmaceutica Sinica ; (12): 550-557, 2014.
Article in Chinese | WPRIM | ID: wpr-245047

ABSTRACT

Base on the Kawakita powder compression equation, a general theoretical model for predicting the compression characteristics of multi-components pharmaceutical powders with different mass ratios was developed. The uniaxial flat-face compression tests of powder lactose, starch and microcrystalline cellulose were carried out, separately. Therefore, the Kawakita equation parameters of the powder materials were obtained. The uniaxial flat-face compression tests of the powder mixtures of lactose, starch, microcrystalline cellulose and sodium stearyl fumarate with five mass ratios were conducted, through which, the correlation between mixture density and loading pressure and the Kawakita equation curves were obtained. Finally, the theoretical prediction values were compared with experimental results. The analysis showed that the errors in predicting mixture densities were less than 5.0% and the errors of Kawakita vertical coordinate were within 4.6%, which indicated that the theoretical model could be used to predict the direct compaction characteristics of multi-component pharmaceutical powders.


Subject(s)
Cellulose , Chemistry , Excipients , Chemistry , Fumarates , Chemistry , Lactose , Chemistry , Models, Chemical , Powders , Chemistry , Pressure , Starch , Chemistry , Technology, Pharmaceutical
19.
Article in English | IMSEAR | ID: sea-163307

ABSTRACT

The matrix metalloproteinase-13 (MMP-13) inhibitory activities of carboxylic acid based compounds, in presence and absence of bovine serum albumin (BSA), have been analyzed quantitatively in terms of chemometric descriptors. The statistically validated quantitative structure-activity relationship (QSAR) models obtained through combinatorial protocol in multiple linear regression (CP-MLR) analysis and the participated descriptors in these models provided rationales to explain the inhibitory activities of these congeners. For MMP-13 inhibition activity, the identified descriptors (BEHm1, BELm1 and BEHm8) have highlighted the role of the atomic mass in terms of the highest and lowest eigenvalues derived from Burden matrix. The positive correlation with activity suggested that their higher values are desirable in improving the activity of a compound. Additionally, the descriptor C-027 representing R-CH-X type fragment in a molecular structure advocates the absence of such type of fragment for the improved activity. On the other hand presence of RCO-N< or >N-X=X type fragment (descriptor N-072) would be beneficiary to the MMP-13 inhibitory activity. The structural features, rationalized by the descriptors MSD (Balaban’s mean square distance index), nCrHR (number of ring tertiary C (sp3), H-047 (H attached to C1(sp3)/C0(sp2)) and H-050 (H attached to heteroatom) have imparted positive impact on the MMP-13 w/BSA inhibition activity. The atomic properties such as atomic polarizability and atomic Sanderson’s electronegativity have shown their positive impact on the activity via descriptors BELp4 and GATS3e in respective eigenvalues or lag. The other descriptors, MATS1m and MATS3e, have revealed the negative influence of atomic mass and electronegativity on the of MMP-13 w/BSA inhibition activity. The results obtained from CP-MLR analysis have been supported further through partial least-squares (PLS) study.


Subject(s)
Carboxylic Acids/analogs & derivatives , Carboxylic Acids/analysis , Carboxylic Acids/metabolism , Enzyme Inhibitors/chemistry , Linear Models , Matrix Metalloproteinase Inhibitors/analysis , Matrix Metalloproteinase Inhibitors/chemistry , Models, Chemical , Molecular Structure , Quantitative Structure-Activity Relationship
20.
Indian J Biochem Biophys ; 2013 Jun; 50(3): 221-226
Article in English | IMSEAR | ID: sea-147306

ABSTRACT

The kinetic mechanism of enzymatic modification of flavonol quercetin with L-cysteine by horseradish peroxidase (HRP) was studied. Reaction of modification of quercetin was followed by recording spectral changes over time at 380 nm. All reactions were performed in 100 mM phosphate buffer pH, 6.0 at 20ºC. Kinetic parameters were determined from graphics of linear Michaelis-Menten equation. The values obtained at specified intervals were: Vmax = 0.17 ÷ 0.91 ΔA380/min, Km = 0.023 ÷ 0.5 mM, kcat = 0.21 ÷ 1.14 ΔA380/min∙nM-1 and Vmax/Km = 0.83 ÷ 26.55 ΔA380/min∙mM-1. It was found that all investigated reactions of the modification of quercetin with L-cysteine by HRP followed an ordered mechanism. We propose that HRP initially reacts with H2O2 than with quercetin and finally with L-cysteine, leading to the introduction of L-cysteine in the structure of quercetin.


Subject(s)
Computer Simulation , Cysteine/chemistry , Enzyme Activation , Horseradish Peroxidase/chemistry , Kinetics , Models, Chemical , Quercetin/chemistry
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