Biochemistry and analytical biochemistry : current research最新文献

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Analysis of the Cytotoxic Effects of Vitamin D3 on Colorectal, Breast andCervical Carcinoma Cell Lines 维生素D3对结直肠癌、乳腺癌和宫颈癌细胞系的细胞毒作用分析
Biochemistry and analytical biochemistry : current research Pub Date : 2017-04-20 DOI: 10.4172/2161-1009.1000318
N. Shruthi, Prashanthkumar Mv, B. Venugopalreddy, Suma Mn, Subba Rao Vm
{"title":"Analysis of the Cytotoxic Effects of Vitamin D3 on Colorectal, Breast andCervical Carcinoma Cell Lines","authors":"N. Shruthi, Prashanthkumar Mv, B. Venugopalreddy, Suma Mn, Subba Rao Vm","doi":"10.4172/2161-1009.1000318","DOIUrl":"https://doi.org/10.4172/2161-1009.1000318","url":null,"abstract":"Although evidences from epidemiological suggested possible involvement of vitamin D in the prevention and treatment of cancers, it is not fully known how vitamin D inhibits cancer cell growth. Recent studies have shown that 1,25-(OH)2D inhibits cancer cell proliferation by binding to vitamin-D receptor (VDR). The vitamin D - VDR complex in turn (a) upregulate cell cycle inhibitors p21 and p27; (b) promote apoptosis mediators caspase-3 and 7, Bad, p53 and PTEN; (c) arrest cells in senescence phase; (d) elevate cell differentiation; and (e) inhibit IGF signaling. Moreover, vitamin D reduces reactive oxygen species (ROS) there by prevents the progression of cancer cells. However, it is currently unknown whether vitamin D induced cancer cell death is mediated by its effect on ROS destroying Nrf2 signaling. In addition, it is also not known whether withdrawal of glucose improves the efficacy of vitamin D as presence of excess glucose promotes ROS in cancer cells. Therefore, first, efficacy of vitamin D for inhibiting the growth of cell lines HCT116, HeLa and MCF-7 was determined. Next, the effect of vitamin D on Nrf2 expression and activity in the presence and absence of glucose was assessed. The data showed that vitamin D inhibited the growth of HCT116, HeLa and MCF-7 cells in a dose dependent manner with more potency toward HCT116. Vitamin D reduced the levels of Nrf2 and NQO1 expression when HCT116 cells were treated in glucose lacking medium. But, despite a significant reduction in cell viability, no change in the Nrf2 expression was observed if the HCT-116 cells were treated with vitamin D dissolved in high glucose (4.5g/L) containing DMEM. Therefore, it is concluded that the cell growth inhibition by vitamin D, observed in the presence of glucose, is not at least mediated by Nrf2 modulation in HCT116 cells.","PeriodicalId":89896,"journal":{"name":"Biochemistry and analytical biochemistry : current research","volume":"6 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2017-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42170141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
A Study in Total Vitamin D Assay 总维生素D测定的研究
Biochemistry and analytical biochemistry : current research Pub Date : 2017-04-19 DOI: 10.4172/2161-1009.1000317
Salwa Al-Refaee, M. Hattab
{"title":"A Study in Total Vitamin D Assay","authors":"Salwa Al-Refaee, M. Hattab","doi":"10.4172/2161-1009.1000317","DOIUrl":"https://doi.org/10.4172/2161-1009.1000317","url":null,"abstract":"A renewed interest in vitamin D reflects almost the high prevalence of vitamin D deficiency worldwide and the increased publication connecting its deficiency to other clinical conditions other than bone health [1]. Therefore, the combination of total vitamin D levels with other tests should be considered when studying certain clinical conditions such as bone diseases and diabetes mellitus [2]. In most assays underestimation of the vitamin levels observed even with the new measurement of total vitamin D (D3+ D2) assay [1,3]. Also reference range for the vitamin around 50 nmol/l was established that is increased as you reach the equator due to increased sun exposure [2]. Assay provided in our country uses 75 nmol/l as reference range, regardless the fact that different assays will produce different results. We studied total vitamin D using two different assays (Roche and diaSorin).","PeriodicalId":89896,"journal":{"name":"Biochemistry and analytical biochemistry : current research","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45743744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hypolipidemic Effects of Irvingia gabonensis - Supplemented Diets inMale Albino Rats 加蓬果补充饲料对雄性白化大鼠的降血脂作用
Biochemistry and analytical biochemistry : current research Pub Date : 2017-04-03 DOI: 10.4172/2161-1009.1000316
S. Kuyooro, E. Abam, Elizabeth Bolaji Agbede
{"title":"Hypolipidemic Effects of Irvingia gabonensis - Supplemented Diets inMale Albino Rats","authors":"S. Kuyooro, E. Abam, Elizabeth Bolaji Agbede","doi":"10.4172/2161-1009.1000316","DOIUrl":"https://doi.org/10.4172/2161-1009.1000316","url":null,"abstract":"Cardiovascular disease has become a disease of global concern. The present study investigated the effect of an Irvingia gabonensis - supplemented diet on cardiovascular disease risk. 24 male albino rats divided into 4 groups of 6 animals each were used. Diets containing varying amounts of Irvingia gabonensis seeds were prepared and fed to the rats for 4 weeks. Lipid profiles of the plasma total cholesterol, triacylglycerol, high-density liporotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol were determined. Generally, Irvingia gabonensis supplementation in diets resulted in reduced organ/body weight ratios. Total cholesterol, LDL-cholesterol levels and artherogenic indices were significantly reduced. The results of this study indicate that Irvingia gabonensis consumption has athero-protective potential as evidenced in the reduction in atherogenic indices in the rats. Results also suggest that the mechanism involved may be through reduction in cholesterol synthesis and transport to the peripheral tissues as observed in the decrease in LDL-cholesterol.","PeriodicalId":89896,"journal":{"name":"Biochemistry and analytical biochemistry : current research","volume":" ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46358311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
A Novel Molecularly Imprinted Polymer for the Selective Removal ofInterfering Hemoglobin Prior to Whole Blood Analysis 一种新型分子印迹聚合物,用于全血分析前选择性去除干扰血红蛋白
Biochemistry and analytical biochemistry : current research Pub Date : 2017-03-27 DOI: 10.4172/2161-1009.1000315
T. H. Tabane, B. Batlokwa
{"title":"A Novel Molecularly Imprinted Polymer for the Selective Removal ofInterfering Hemoglobin Prior to Whole Blood Analysis","authors":"T. H. Tabane, B. Batlokwa","doi":"10.4172/2161-1009.1000315","DOIUrl":"https://doi.org/10.4172/2161-1009.1000315","url":null,"abstract":"A heavy red globular protein, hemoglobin, responsible for whole blood red pigmentation often interferes with the identification and quantification of disease associated biomarkers from whole blood, in field of molecular diagnosis. The main challenge is the direct introduction of whole blood as a sample into analyzing instruments because of its physiological complexity and `dirty` nature. For example, the red pigment in whole blood, which is characterized as ‘dirt’, usually co-elute with the biomarkers and masks them from easy chromatographic separation prior to their final detection. It also clogs the instrument’s components such as the separating columns which are known to be sensitive, hence leading to imprecise and inaccurate results during bio-assaying. To address these challenges, our lab synthesised a novel, selective, effective and a robust hemoglobin imprinted polymer, in the form of a powder, through bulk, freeradical polymerization employing molecular imprinting technology, to selectively remove interfering hemoglobin from whole blood samples prior to instrumental analysis of disease associated biomarkers. From the results, the polymer powder effectively removed hemoglobin from whole blood sample as demonstrated by the ultraviolet-visible absorbance reduction from as high as 0.794 Au to lower values of 0.193 Au before and after polymer powder application, respectively. Experimentally, the powder had a high binding ability towards the targeted hemoglobin as demonstrated by the high percentage removal efficiency of 76% from hemoglobin standard solutions, when compared to its low binding ability towards an analogous species, (chlorophyll), at 32% from chlorophyll standard solutions. Furthermore, the polymer powder proved to be robust as it removed hemoglobin interference from the ‘dirty’ complex matrix of real human whole blood samples by up to 74% hemoglobin removal which was comparable to 76% hemoglobin removal from neat standards, thus, the polymer powder demonstrated that it can work effectively in diverse environments of clean and dirty matrix. Furthermore, the polymer powder presented itself as an efficient, selective and non-destructive whole blood clean-up pre-analytical tool that with further research may replace the destructive and non-selective conventional whole blood clean-up strategies such as the commonly employed centrifugation.","PeriodicalId":89896,"journal":{"name":"Biochemistry and analytical biochemistry : current research","volume":"6 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2017-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1009.1000315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70555663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Optimized Analytical Techniques for Extraction and Separation ofBioactive Compounds from Diverse Plant Types 不同植物中生物活性化合物提取分离的优化分析技术
Biochemistry and analytical biochemistry : current research Pub Date : 2017-03-27 DOI: 10.4172/2161-1009.1000313
M. Suparna, A. Biswas
{"title":"Optimized Analytical Techniques for Extraction and Separation ofBioactive Compounds from Diverse Plant Types","authors":"M. Suparna, A. Biswas","doi":"10.4172/2161-1009.1000313","DOIUrl":"https://doi.org/10.4172/2161-1009.1000313","url":null,"abstract":"Bioactive compounds (BACs) from plants provide unlimited opportunities for pharmaceuticals and natural agrochemicals development due to vast diversity of secondary compounds. Successful identification and development of natural products from plants necessitates a standard and integrated approach to screen compounds which aids in determination of dose response activity. We examined Peperomia pellucida (herb with fibrous root), Cleome viscosa (herb with tap root), Piper chaba (climber) and Artocarpus lakoocha (tree). In C. viscosa plants, BACs were collected from ‘Root Exudates Trapping System’ made of Buchner funnel and conical flask, while compounds were collected from P. pellucida by a self-designed horizontal tube like glass ware with stopper and funnel at either end. BACs are extracted from stem and leaves dust of P. chaba and A. lakoocha respectively. The basic sequential steps are same included grinding of plant parts, homogenization, vacuum filtration followed by liquid-liquid extraction in which BACs were fractionated into two major phases (ethyl acetate layer and aqueous layer). The extracts were further purified into a single pure compound by repetitive running through column and subsequently followed by thin layer chromatography and finally subjected to spectral analyses (viz. MS, IR, 1HNMR and 13CNMR) for complete molecular characterization. A new Phenol glycoside was isolated from Peperomia pellucida and Lactam nonanoic acid was recovered from Cleome viscosa. Four major compounds were recovered from Piper chaba and Artocarpus lakoocha with remarkable bioactivity but only the important fractions are described here. These new extraction techniques will extend and enhance the usefulness of plants as renewable resources of valuable chemicals.","PeriodicalId":89896,"journal":{"name":"Biochemistry and analytical biochemistry : current research","volume":"6 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2017-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1009.1000313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70555563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Traditional Medicine Based Drug Development 以传统医学为基础的药物开发
Biochemistry and analytical biochemistry : current research Pub Date : 2017-03-06 DOI: 10.4172/2161-1009.1000311
P. Perera
{"title":"Traditional Medicine Based Drug Development","authors":"P. Perera","doi":"10.4172/2161-1009.1000311","DOIUrl":"https://doi.org/10.4172/2161-1009.1000311","url":null,"abstract":"Currently few of traditional medicines have been developed by blending basic sciences and technologies up to the clinical usage. In future standard traditional medicine based botanical therapeutics will be important in biomedicine developments due to economic background in most parts of the world. Today there are many basic experimental research have being doing for plant based materials. But very limited data can be founded for evidence based use of those experimented plant materials in clinical setup. Therefore this is the high time for develop effective evidence based traditional medicine system in the world. This can be done by evaluating traditional medicine remedies for their pharmacodynamics, pharmacokinetics, stability, shelf life and toxicity par with current standards. Challenge of reproducibility and consistency of herbal remedies can be achieved by developing standard assay markers and chemiinformatic approaches. Further conventional concepts of clinical research design methods may not be adequate when evaluating and conducting clinical trials for traditional medicine. Therefore needs to identifying traditional medicine concepts and develop research strategies for achieve full benefits of these medicine systems. Further there is need to develop and validate a range of parameters applicable to modern and traditional medicines in the light of basic sciences like biochemistry and molecular biology.","PeriodicalId":89896,"journal":{"name":"Biochemistry and analytical biochemistry : current research","volume":" ","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1009.1000311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49369722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Graphene: A Building Foundation for Efficient Plasmonic SERS Device 石墨烯:高效等离子体SERS器件的构建基础
Biochemistry and analytical biochemistry : current research Pub Date : 2017-03-06 DOI: 10.4172/2161-1009.1000310
G. Das, M. Moretti, B. Torre, M. Allione, A. Giugni, E. Fabrizio
{"title":"Graphene: A Building Foundation for Efficient Plasmonic SERS Device","authors":"G. Das, M. Moretti, B. Torre, M. Allione, A. Giugni, E. Fabrizio","doi":"10.4172/2161-1009.1000310","DOIUrl":"https://doi.org/10.4172/2161-1009.1000310","url":null,"abstract":"In this paper graphene over SiO2/Si substrate was used as a building base to fabricate SERS device. A thin film of silver was deposited over graphene and annealed at 250°C. The substrate was examined after chemisorption of two molecules; rhodamine 6G which is a fluorescent dye, and 3-mercaptobenzoic acid, a thiol molecule. SERS enhancement factor for the proposed device is estimated to be 2.1 × 106 with respect to the flat silver substrate deposited over Si. The experimental results were compared in two ways: a) by using electromagnetic field calculation and b) quantum mechanical calculation derived from density function theory. The experimental findings were consistent with the theoretical observations.","PeriodicalId":89896,"journal":{"name":"Biochemistry and analytical biochemistry : current research","volume":"6 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1009.1000310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46213841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Evaluation of Antibacterial, Antifungal and Phytochemical Screening ofSolanum nigrum 黑胡椒的抗菌、抗真菌和植物化学筛选评价
Biochemistry and analytical biochemistry : current research Pub Date : 2017-02-10 DOI: 10.4172/2161-1009.1000309
K. B. Dar, A. Bhat, S. Amin, M. Zargar, A. Masood, A. H. Malik, S. Ganie
{"title":"Evaluation of Antibacterial, Antifungal and Phytochemical Screening ofSolanum nigrum","authors":"K. B. Dar, A. Bhat, S. Amin, M. Zargar, A. Masood, A. H. Malik, S. Ganie","doi":"10.4172/2161-1009.1000309","DOIUrl":"https://doi.org/10.4172/2161-1009.1000309","url":null,"abstract":"The present study aimed at evaluating the antimicrobial potential of aqueous and methanolic extracts of Solanum nigrum, a traditionally used medicinal plant with multiple therapeutic properties. The susceptibility of microbial strains to the two extracts was determined using agar well diffusion method. The bacterial strains employed were Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus vulgaris and Escherichia coli. The fungal strains used were Penicillium Chrysogenum, Aspergillus fumigatus, Candida albicans and Saccharomyces cerevisiae. Phytochemical screening was performed using standard methods. A dose dependent increase in the antibacterial activity was observed with both the methanol and aqueous extracts. Highest antibacterial activity was exhibited by aqueous extract with Escherichia coli (16 ± 0.23 mm) followed by Staphylococcus aureus (15 ± 0.15 mm) at the concentration of 100 mg/ml plant extract. Methanolic extract showed highest antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa with zone of inhibition (14 ± 0.11 mm) and (14 ± 0.26 mm) at the same concentration (100 mg/ml) respectively. The highest antifungal potential was exhibited by the methanolic extract against Saccharomyces cerevisiae (26 ± 0.27 mm) and Candida albicans (22 ± 0.13 mm), while the aqueous extract exhibits the highest antifungal potential against Saccharomyces cerevisiae (23 ± 0.14 mm) followed by Candida albicans (21 ± 0.10 mm) and Aspergillus fumigatus (16 ± 0.11 mm) at the concentration of 100 mg/ml. Phytochemical analysis revealed the plant is rich in various secondary metabolites like alkaloids, saponins, flavonoids, phenols and volatile oils. Cardenolides and phlobtannins were found absent. The study concludes that the plant possess novel compounds with significant antibacterial and antifungal properties. Isolation and characterization of these novel compounds could provide potent antimicrobial agents to combat pathogenic infections.","PeriodicalId":89896,"journal":{"name":"Biochemistry and analytical biochemistry : current research","volume":" ","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2017-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1009.1000309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49457434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Escherichia coli Generate Oxidative Stress and Enhance Lipid Peroxidationin the Kidney of the Rat 大肠杆菌引起大鼠肾脏氧化应激并促进脂质过氧化
Biochemistry and analytical biochemistry : current research Pub Date : 2017-01-24 DOI: 10.4172/2161-1009.1000306
Amiy Dutt Chaturvedi, K. Nagarajan, D. Pal, Awanish Kumar
{"title":"Escherichia coli Generate Oxidative Stress and Enhance Lipid Peroxidationin the Kidney of the Rat","authors":"Amiy Dutt Chaturvedi, K. Nagarajan, D. Pal, Awanish Kumar","doi":"10.4172/2161-1009.1000306","DOIUrl":"https://doi.org/10.4172/2161-1009.1000306","url":null,"abstract":"The urinary tract is generally infected by Escherichia coli bacteria. They commonly originate in the patient's own bowel, and infection occurs mostly via the ascending route. In this study, we have observed the influence of E. coli on oxidative stress generation and lipid peroxidation in the kidney of the rat. E. coli were taken from the soil, urine, buffalo intestine and goat intestine for this study. Rats were infected with isolated E. coli from different sources and Lipid peroxidation, glutathione assay was done to achieve the goal of this study. Percentage survival data showed that the E. coli isolated from urine had more lethargy phenomena because their survival present was 66.66% and the mortality rate was higher in this group. Although E. coli isolated from Goat intestine has also shown the same mortality, but the E. coli isolated from urine sample shown this mortality from the second day whereas the E. coli isolated from goat intestine from the third day. By and large data indicated that the E. coli isolated from urine sample generated high oxidative stress and damage rat kidney because the kidney is an organ frequently exposed to oxidative stress. Overall, free radical generated due to E. coli infection further enhances lipid peroxidation in the rat which is harmful to the physiology because it may cause a renal disorder in the rat.","PeriodicalId":89896,"journal":{"name":"Biochemistry and analytical biochemistry : current research","volume":"6 1","pages":"0-0"},"PeriodicalIF":0.0,"publicationDate":"2017-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1009.1000306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44113208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
E-Pharmacophore Model Assisted Discovery of Novel Antagonists ofnNOS 电子载体模型辅助发现新型一氧化氮合酶拮抗剂
Biochemistry and analytical biochemistry : current research Pub Date : 2017-01-24 DOI: 10.4172/2161-1009.1000307
N. R. Madhulitha, N. Pradeep, S. Swargam, eep, K. Hema, P. Chiranjeevi, Katari Sudheer Kumar, A. Umamaheswari
{"title":"E-Pharmacophore Model Assisted Discovery of Novel Antagonists ofnNOS","authors":"N. R. Madhulitha, N. Pradeep, S. Swargam, eep, K. Hema, P. Chiranjeevi, Katari Sudheer Kumar, A. Umamaheswari","doi":"10.4172/2161-1009.1000307","DOIUrl":"https://doi.org/10.4172/2161-1009.1000307","url":null,"abstract":"The nitric oxide (NO) synthesized by neuronal nitric oxide synthase (nNOS) acts as a neurotransmitter and plays a crucial role in a series of neurobiological functions. In diseased condition, activated nNOS induces nitrosylation as well as phosphorylation of tau protein and glycogen synthase kinase 3 beta (GSK-3β) respectively. Hyper phosphorylation of tau accelerates tau oligomerization resulting in formation of neurofibrillary tangles (NFT), ensuring the neuronal cell death in hippocampus region; a hallmark of Alzheimer’s disease (AD). Thus, designing inhibitor towards nNOS may reduce the neuronal loss caused by nNOS. Hence nNOS has been one of the revitalizing targets for AD. In the present work, one energetically optimized structure-based pharmacophore (e-pharmacophore) was generated using nNOS co-crystal structure (4D1N) to map important pharmacophoric features of nNOS. Shape based similarity screening performed using e-pharmacophore against in-house library of more than one million compounds resulted 2701 library of compounds. Rigid receptor docking (RRD) was applied and followed by molecular mechanics and generalized Born and surface area (MM-GBSA) calculation which results 22 nNOS ligands. To define the leads, dock complexes were subjected to quantum-polarized ligand docking (QPLD) followed by free energy calculations revealed 3 leads. On comparison with 1 existing inhibitor,it concealed three best leads with lower binding energy and better binding affinity. The best lead was subjected to induced fit docking (IFD) with MM-GBSA calculation and further molecular dynamics (MD) simulations for 50 ns in solvated model system. Potential energy, root mean square deviation (RMSD) and root mean square fluctuations (RMSF) results disclosed constancy of lead 1 interactions throughout 50 ns MD simulations run. Thus proposed three leads are having favorable absorption distribution metabolism excretion toxicity (ADME/T) properties and provide a scaffold for designing nNOS antagonists.","PeriodicalId":89896,"journal":{"name":"Biochemistry and analytical biochemistry : current research","volume":"6 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2017-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1009.1000307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44157082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
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