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101.
Acetazolamide Inhibits the Level of Tyrosinase and Melanin: An Enzyme Kinetic,In Vitro,In Vivo,and In Silico Studies 下载免费PDF全文
Melanin is the major factor that determines skin color and protects from ultraviolet radiation. In present study we evaluated the anti‐melanogenesis effect of acetazolamide (ACZ) using four different approaches: enzyme kinetic, in vitro, in vivo and in silico. ACZ demonstrated significant inhibitory activity (IC50 7.895 ± 0.24 μm ) against tyrosinase as compared to the standard drug kojic acid (IC50 16.84 ± 0.64 μm ) and kinetic analyses showed that ACZ is a non‐competitive inhibitor without cytotoxic effect. In in vitro experiments, A375 human melanoma cells were treated with 20 or 40 μm of ACZ with or without 50 μm of l ‐DOPA. Western blot results showed that ACZ significantly (P < 0.05) decreased the expression level of tyrosinase at 40 μm . Zebrafish embryos were treated with 10, 20 or 40 μm of ACZ and of positive control kojic acid. At 72 h of treatment with ACZ and kojic acid, ACZ significantly (P < 0.001) decreased the embryos pigmentation to 40.8% of untreated embryos at the dose of 40 μm of ACZ while kojic acid decreased only 25.0% of pigmentation at the same dose of kojic acid. In silico docking were performed against tyrosinase using PyRx tool. Docking studies suggested that His244, Asn260 and His85 are the major interacting residues in the binding site of the protein. In conclusion, our results suggest that ACZ is a good candidate for the inhibition of melanin and it could be used as a lead for developing the drugs for hyperpigmentary disorders and skin whitening. 相似文献
102.
Faiyaz Shakeel Sanjula Baboota Alka Ahuja Javed Ali Sheikh Shafiq 《Journal of nanobiotechnology》2008,6(1):1-11
Background
Celecoxib, a selective cyclo-oxygenase-2 inhibitor has been recommended orally for the treatment of arthritis and osteoarthritis. Long term oral administration of celecoxib produces serious gastrointestinal side effects. It is a highly lipophilic, poorly soluble drug with oral bioavailability of around 40% (Capsule). Therefore the aim of the present investigation was to assess the skin permeation mechanism and bioavailability of celecoxib by transdermally applied nanoemulsion formulation. Optimized oil-in-water nanoemulsion of celecoxib was prepared by the aqueous phase titration method. Skin permeation mechanism of celecoxib from nanoemulsion was evaluated by FTIR spectral analysis, DSC thermogram, activation energy measurement and histopathological examination. The optimized nanoemulsion was subjected to pharmacokinetic (bioavailability) studies on Wistar male rats.Results
FTIR spectra and DSC thermogram of skin treated with nanoemulsion indicated that permeation occurred due to the disruption of lipid bilayers by nanoemulsion. The significant decrease in activation energy (2.373 kcal/mol) for celecoxib permeation across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (p < 0.05). Photomicrograph of skin sample showed the disruption of lipid bilayers as distinct voids and empty spaces were visible in the epidermal region. The absorption of celecoxib through transdermally applied nanoemulsion and nanoemulsion gel resulted in 3.30 and 2.97 fold increase in bioavailability as compared to oral capsule formulation.Conclusion
Results of skin permeation mechanism and pharmacokinetic studies indicated that the nanoemulsions can be successfully used as potential vehicles for enhancement of skin permeation and bioavailability of poorly soluble drugs. 相似文献103.
Rehman S Shawl AS Verma V Kour A Athar M Andrabi R Sultan P Qazi GN 《Prikladnaia biokhimiia i mikrobiologiia》2008,44(2):225-231
The medicinal plant, Nothapodytes foetida contains a number of important alkaloids like camptothecin (an anticancer drug molecule) but its concentration is less to meet the existing demand of this important molecule, so in an effort for accessible availability of camptothecin. An endophyte (designated ZP5SE) was isolated from the seed of Nothapodytes foetida and was examined as potential source of anticancer drug lead compound i.e. camptothecin, when grown in Sabouraud liquid culture media under shake flask conditions. The presence of anticancer compound (camptothecin) in this fungus was confirmed by chromatographic and spectroscopic methods in comparison with authentic camptothecin. Isolated endophyte (Neurospora crassa) producing camptothecin may become an easily accessible source for the production of precursor anticancer drug molecule in future at large scale. 相似文献
104.
Muhammad Ayub Sulman Basit Fazal Ur Rehman Masoom Yasinzai 《American journal of human genetics》2009,85(4):515-520
Desmosomes are the major players in epidermis and cardiac muscles and contribute to intercellular binding and maintenance of tissue integrity. Two important constituents of desmosomes are transmembrane cadherins named desmogleins and desmocollins. The critical role of these desmosomal proteins in epithelial integrity has been illustrated by their disruption in mouse models and human diseases. In the present study, we have investigated a large family from Afghanistan in which four individuals are affected with hereditary hypotrichosis and the appearance of recurrent skin vesicle formation. All four affected individuals showed sparse and fragile hair on scalp, as well as absent eyebrows and eyelashes. Vesicles filled with thin, watery fluid were observed on the affected individuals'' scalps and on most of the skin covering their bodies. A scalp-skin biopsy of an affected individual showed mild hair-follicle plugging. Candidate-gene-based homozygosity linkage mapping assigned the disease locus to 8.30 cM (8.51 Mbp) on chromosome 18q12.1. A maximum multipoint LOD score of 3.30 (θ = 0.00) was obtained at marker D18S877. Sequence analysis of four desmoglein and three desmocollin genes, contained within the linkage interval, revealed a homozygous nonsense mutation (c.2129T>G [p.Leu710X]) in exon-14 of the desmocollin-3 (DSC3) gene. 相似文献
105.
In single-celled spores of the fern Ceratopteris richardii, gravity directs polarity of development and induces a directional, trans-cellular calcium (Ca2+) current. To clarify how gravity polarizes this electrophysiological process, we measured the kinetics of the cellular response
to changes in the gravity vector, which we initially estimated using the self-referencing calcium microsensor. In order to
generate more precise and detailed data, we developed a silicon microfabricated sensor array which facilitated a lab-on-a-chip
approach to simultaneously measure calcium currents from multiple cells in real time. These experiments revealed that the
direction of the gravity-dependent polar calcium current is reversed in less than 25 s when the cells are inverted, and that
changes in the magnitude of the calcium current parallel rapidly changing g-forces during parabolic flight on the NASA C-9 aircraft. The data also revealed a hysteresis in the response of cells in
the transition from 2g to micro-g in comparison to cells in the micro-g to 2-g transition, a result consistent with a role for mechanosensitive ion channels in the gravity response. The calcium current
is suppressed by either nifedipine (calcium-channel blocker) or eosin yellow (plasma membrane calcium pump inhibitor). Nifedipine
disrupts gravity-directed cell polarity, but not spore germination. These results indicate that gravity perception in single
plant cells may be mediated by mechanosensitive calcium channels, an idea consistent with some previously proposed models
of plant gravity perception. 相似文献
106.
Husain Q Ansari SA Alam F Azam A 《International journal of biological macromolecules》2011,49(1):37-43
The present study demonstrates the immobilization of Aspergillus oryzae β galactosidase on native zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO-NP) by simple adsorption mechanism. The binding of enzyme on ZnO-NP was confirmed by Fourier transform-infrared spectroscopy and atomic force microscopy. Native ZnO and ZnO-NP showed 60% and 85% immobilization yield, respectively. Soluble and immobilized enzyme preparations exhibited similar pH-optima at pH 4.5. ZnO-NP bound β galactosidase retained 73% activity at pH 7.0 while soluble and ZnO adsorbed enzyme lost 68% and 53% activity under similar experimental conditions, respectively. There was a marked broadening in temperature-activity profile for ZnO-NP adsorbed β galactosidase; it showed no difference in temperature-optima between 50 °C and 60 °C. Moreover, ZnO-NP adsorbed β galactosidase retained 53% activity after 1 h incubation with 5% galactose while the native ZnO- and soluble β galactosidase exhibited 35% and 28% activity under similar exposure, respectively. Native ZnO and ZnO-NP adsorbed β galactosidase retained 61% and 75% of the initial activity after seventh repeated use, respectively. It was noticed that 54%, 63% and 71% milk lactose was hydrolyzed by soluble, ZnO adsorbed and ZnO-NP adsorbed β galactosidase in batch process after 9 h while whey lactose was hydrolyzed to 61%, 68% and 81% under similar experimental conditions, respectively. In view of its easy production, improved stability against various denaturants and excellent reusability, ZnO-NP bound β galactosidase may find its applications in constructing enzyme-based analytical devices for clinical, environmental and food technology. 相似文献
107.
The risk posed by the quantity of heavy metal lead present in Ca supplements is of grave concern. Some lead levels have been
measured up to the extent of regulatory limit set by the United States. Calcium supplements inevitably get contaminated with
lead as both are naturally occurring elements having the same charge density. Therefore, it is imperative to indicate the
level of this toxic metal in these supplements in order to create awareness among consumers. The calcium in the supplements
is derived from natural as well as synthetic/refined sources (chelated or non-chelated). In this study, a sophisticated analytical
technique, atomic absorption spectrometer (both with FAAS and GFAAS modes of atomization), was used for the purpose of analyzing
Pb contents in 27 commonly used Ca supplements manufactured by different national and multinational companies. The daily intake
of lead through these supplements was calculated. Only 10% of the calcium supplements analyzed met the criteria of acceptable
Pb levels (1.5 μg/daily dose) in supplements/consumer products set by the United States. It was also found that Pb intake
was highest in chelated calcium supplements whereas lowest through calcium supplements with vitamin D formulation. The Pb
concentration in calcium supplements was significantly increased (p < 0.001) according to their composition. In order to validate our results from the study conducted, IAEA-certified reference
material (animal bone, H-5) was analyzed for Pb levels. The limit of detection of the method used was 0.05 μg/g and a 95%
lead recovery of IAEA-certified reference material (animal bone, H-5). 相似文献
108.
We present a novel partner‐specific protein–protein interaction site prediction method called PAIRpred. Unlike most existing machine learning binding site prediction methods, PAIRpred uses information from both proteins in a protein complex to predict pairs of interacting residues from the two proteins. PAIRpred captures sequence and structure information about residue pairs through pairwise kernels that are used for training a support vector machine classifier. As a result, PAIRpred presents a more detailed model of protein binding, and offers state of the art accuracy in predicting binding sites at the protein level as well as inter‐protein residue contacts at the complex level. We demonstrate PAIRpred's performance on Docking Benchmark 4.0 and recent CAPRI targets. We present a detailed performance analysis outlining the contribution of different sequence and structure features, together with a comparison to a variety of existing interface prediction techniques. We have also studied the impact of binding‐associated conformational change on prediction accuracy and found PAIRpred to be more robust to such structural changes than existing schemes. As an illustration of the potential applications of PAIRpred, we provide a case study in which PAIRpred is used to analyze the nature and specificity of the interface in the interaction of human ISG15 protein with NS1 protein from influenza A virus. Python code for PAIRpred is available at http://combi.cs.colostate.edu/supplements/pairpred/ . Proteins 2014; 82:1142–1155. © 2013 Wiley Periodicals, Inc. 相似文献
109.
Abdul Wadood Muhammad Riaz Amir ul Mulk Momin Khan Sobia Ahsan Haleem Sulaiman Shams Sahib Gul Ayaz Ahmed Muhammad Qasim Farman Ali Zaheer Ul-Haq 《Bioinformation》2014,10(5):299-307
Urease is an important enzyme both in agriculture and medicine research. Strategies based on urease inhibition is critically
considered as the first line treatment of infections caused by urease producing bacteria. Since, urease possess agro-chemical and
medicinal importance, thus, it is necessary to search for the novel compounds capable of inhibiting this enzyme. Several
computational methods were employed to design novel and potent urease inhibitors in this work. First docking simulations of
known compounds consists of a set of arylidine barbiturates (termed as reference) were performed on the Bacillus pasteurii (BP)
urease. Subsequently, two fold strategies were used to design new compounds against urease. Stage 1 comprised of the energy
minimization of enzyme-ligand complexes of reference compounds and the accurate prediction of the molecular mechanics
generalized born (MMGB) interaction energies. In the second stage, new urease inhibitors were then designed by the substitution
of different groups consecutively in the aryl ring of the thiobarbiturates and N, N-diethyl thiobarbiturates of the reference ligands..
The enzyme-ligand complexes with lowest interaction energies or energies close to the calculated interaction energies of the
reference molecules, were selected for the consequent chemical manipulation. This was followed by the substitution of different
groups on the 2 and 5 positions of the aryl ring. As a result, several new and potent diethyl thiobarbiturates were predicted as
urease inhibitors. This approach reflects a logical progression for early stage drug discovery that can be exploited to successfully
identify potential drug candidates. 相似文献
110.
Muhammad Muzammal Adeel Muhammad Qasim Usman Ali Ashfaq Muhammad Shareef Masoud Mahmood ur Rehman Muhammad Tahir ul Qamar Muhammad Rizwan Javed 《Bioinformation》2014,10(7):454-459
Computational tools occupy the prime position in the analysis of large volume of post-genomic data. These tools have advantage
over the wet lab experiments in terms of high coverage, cost and time. Breast cancer is the most common cancer in females
worldwide. It is a genetically heterogeneous disorder and many genes are involved in the pathway of the disease. Mutations in
metastasis suppressor gene are the major cause of the disease. In this study, the effects of mutations in breast cancer metastasis
suppressor 1gene upon protein structure and function were examined by means of computational tools and information from
databases.This study can be useful to predict the potential effect of every allelic variant, devise new biological experiments and to
interpret and predict the patho-physiological impact of new mutations or non-synonymous polymorphisms. 相似文献