Dual targeted 2-Benzylideneindanone pendant hydroxamic acid group exhibits selective HDAC6 inhibition along with tubulin stabilization effect.

Abnormal epigenetics has been recognised as an early event in tumour progression and aberrant acetylation of lysine in particular has been understood in tumorigenesis. Therefore, it has become an attractive target for anticancer drug development. However, HDAC inhibitors have limited success due to toxicity and drug resistance concerns. Present study deals with design and synthesis of bivalent indanone based HDAC6 and antitubulin ligands as anticancer agents. Two of the analogues 9 and 21 exhibited potent antiproliferative activities (IC50, 0.36-3.27 µM) and high potency against HDAC 6 enzyme. Compound 21 showed high selectivity against HDAC 6 while 9 exhibited low selectivity. Both the compounds also showed microtubule stabilization effects and moderate anti-inflammatory effect. Dual targeted anticancer agents with concomitant anti-inflammatory effects will be more attractive clinical candidates in future.

Compressibility of structural modulation waves in the chain compounds BaCoX2O7 (X = As, P): a powder study.

BaCoX2O7 (X = As, P) are built on magnetic 1D units in which strong aperiodic undulations originate from incommensurate structural modulations with large atomic displacive amplitudes perpendicular to the chain directions, resulting in very unique multiferroic properties. High-pressure structural and vibrational properties of both compounds have been investigated by synchrotron X-ray powder diffraction and Raman spectroscopy at room temperature and combined with density functional calculations. A structural phase transition is observed at 1.8 GPa and 6.8 GPa in BaCoAs2O7 and BaCoP2O7, respectively. Sharp jumps are observed in their unit-cell volumes and in Raman mode frequencies, thus confirming the first-order nature of their phase transition. These transitions involve the disappearance of the modulation from the ambient-pressure polymorph with clear spectroscopic fingerprints, such as reduction of the number of Raman modes and change of shape on some peaks. The relation between the evolution of the Raman modes along with the structure are presented and supported by density functional theory structural relaxations.

Microtubule associated proteins as targets for anticancer drug development.

The dynamic equilibrium of tubulin-microtubule is an essential aspect of cell survivality. Modulation of this dynamics has become an important target for the cancer drug development. Tubulin exists in the alpha-beta dimer form which polymerizes to form microtubule and further depolymerizes back to tubulin dimer. The microtubule plays an essential role in mitosis and cell multiplication. Antitubulin drugs disturb the microtubule dynamics which is essentially required for DNA segregation and cell division during mitosis so killing the cancerous cells. Microtubule Associated Proteins (MAPs) interact with cellular cytoskeletal microtubules. MAPs bind to the either polymerized or depolymerized tubulin dimers within the cell and mostly causing stabilization of microtubules. Some of the tubulin binding drugs are in clinical use and others in clinical trial. MAPs inhibitors are also in clinical trial. Post-translational modification of lysine-40 either in histone or in alpha tubulin has an important role in gene expression and is balanced between histone deacetylases (HDACs) and histone acetyltransferases (HATs). HDAC inhibitors have the anticancer properties to form a drug for the treatment of cancer. They act by inducing cell cycle arrest and cell death. Some of the HDAC inhibitors are approved to be used as anticancer drug while others are under different phases of clinical trial. The present review updates on various MAPs, their role in cancer progression, MAPs inhibitors and their future prospects.

Enzymatic hydrolysis of native granular starches by a new ß-amylase from peanut (Arachis hypogaea).

The present work describes efficient hydrolysis of native starch by a novel ß-amylase from peanut (Arachis hypogaea). The Dextrose Equivalent value, which is a measure of starch hydrolysis, for potato and corn starch increased significantly by 40% and 10%, respectively, releasing maltose. Scanning electron microscopy revealed that enzymatic corrosion occurred mainly at the surface of starch granules, leaving broken granules to smaller particles at later stage of digestion. Further, X-ray analysis and Fourier transform infrared spectroscopy displayed the loss of ordered structure in the enzyme degraded starches. These results described the pattern of hydrolysis. Since the action of already known plant ß-amylases (sweet potato and soybean) on native starch granule is not very effective and requires gelatinization for maltose production, ß-amylase from peanut could be a useful alternative in the present endeavor. It would potentially save time and money arising from gelatinization and lead to improvements in industrial maltose production.

An antioxidant rich novel ß-amylase from peanuts (Arachis hypogaea): Its purification, biochemical characterization and potential applications.

ß-Amylase from un-germinated seeds of peanut (Arachis hypogaea) was purified to apparent electrophoretic homogeneity with final purification fold of 205 and specific activity of 361µmol/min/mg protein. The enzyme was purified employing simple purification techniques for biochemical characterization. The purified enzyme was identified as ß-amylase with Mr of 31kDa. The enzyme displayed its optimum catalytic activity at pH5.0 and 60°C with activation energy of 4.5kcal/mol and Q10 1.2. The enzyme displayed Km and Vmax values, for soluble potato starch of 1.28mg/mL and 363.63µmol/min/mg, respectively. Thermal inactivation of ß-amylase at 65°C resulted into first-order kinetics with rate constant 0.0126min-1 and t½ 55min. The enzyme was observed to act on native granular potato starch, which could minimize the high cost occurring from solubilization of starch in industries. Enzyme fractions scavenge 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical, indicating its antioxidative nature. In addition, the purified ß-amylase was successfully utilized for the improvement of antioxidant potential of wheat. These findings suggest that ß-amylase from peanuts have potential application in food and pharmaceutical industries.

Covalent immobilization of peanut ß-amylase for producing industrial nano-biocatalysts: A comparative study of kinetics, stability and reusability of the immobilized enzyme.

Stability of enzymes is an important parameter for their industrial applicability. Here, we report successful immobilization of ß-amylase (bamyl) from peanut (Arachis hypogaea) onto Graphene oxide-carbon nanotube composite (GO-CNT), Graphene oxide nanosheets (GO) and Iron oxide nanoparticles (Fe3O4). The Box-Behnken Design of Response Surface Methodology (RSM) was used which optimized parameters affecting immobilization and gave 90%, 88% and 71% immobilization efficiency, respectively, for the above matrices. ß-Amylase immobilization onto GO-CNT (bamyl@GO-CNT) and Fe3O4 (bamyl@Fe3O4), resulted into approximately 70% retention of activity at 65 °C after 100 min of exposure. We used atomic force microscopy (AFM), scanning and transmission electron microscopy (SEM and TEM), Fourier transformed infrared (FT-IR) spectroscopy and fluorescence microscopy for characterization of free and enzyme bound nanostructures (NS). Due to the non-toxic nature of immobilization matrices and simple but elegant immobilization procedure, these may have potential utility as industrial biocatalysts for production of maltose.

Critical, agentic and trans-media: Frameworks and findings from a foresight analysis exercise on audiences.

We write this article presenting frameworks and findings from an international network on audience research, as we stand 75 years from Herta Herzog's classic investigation of radio listeners, published in Lazarsfeld and Stanton's 1944 war edition of Radio Research. The article aims to contribute to and advance a rich strand of self-reflexive stock-taking and sorting of future research priorities within the transforming field of audience analysis, by drawing on the collective efforts of CEDAR - Consortium on Emerging Directions in Audience Research - a 14-country network (2015-2018) funded by the Arts and Humanities Research Council, United Kingdom, which conducted a foresight analysis exercise on developing current trends and future scenarios for audiences and audience research in the year 2030. First, we wish to present the blueprint of what we did and how we did it - by discussing the questions, contexts and frameworks for our project. We hope this is useful for anyone considering a foresight analysis task, an approach we present as an innovative and rigorous tool for assessing and understanding the future of a field. Second, we present findings from our analysis of pivotal transformations in the field and the future scenarios we constructed for audiences, as media technologies rapidly change with the arrival of the Internet of Things and changes on many levels occur in audience practices. These findings not only make sense of a transformative decade that we have just lived through but they present possibilities for the future, outlining areas for individual and collective intellectual commitment.

Development of a mathematical model to predict different parameters during pharmaceutical wastewater treatment using TiO2 coated membrane.

The aim of present study is to develop a mathematical model to understand the photomineralization process for an antiseptic drug component, chlorhexidine digluconate using catalytic membrane. Overall process was executed in a photo reactor with immobilized TiO2 nanoparticles on the membrane surface, which gives the better recovery and reuse of the catalyst. To assess the overall process performance, a mathematical model has been developed for prediction of substrate concentration in the permeate stream and the theoretical build-up of the polarized layer in case of a membrane coated with TiO2 nanoparticles. In the developed mathematical model, the governing partial differential equation was solved with the help of initial boundary condition over the concentration boundary layer and Kozeny-Carmen equation. In this model the simultaneous change in the active surface area and the polarized layer thickness with the change in substrate concentration in the boundary layer was incorporated to enhance the accuracy of the model. The resulting non-linear partial differential equation, coupled with other non-linear ordinary differential equation is solved using Runga Kutta fourth order method. Average deviation between theoretical results and the experimental data generated in this study was found to remain within ±5% and precision level was maintained at 0.01%.