Selective Binding of Cyclodextrins with Leflunomide and Its Pharmacologically Active Metabolite Teriflunomide

The selectivity of encapsulation of leflunomide and teriflunomide by native α-, β- and γ-cyclodextrins was investigated through ¹H NMR and molecular modeling. Thermodynamic analysis revealed the main driving forces involved in the binding. For α-cyclodextrin, the partial encapsulation was obtained while deep penetration was characterized for the other two cyclodextrins, where the remaining polar fragment of the molecule is located outside the macrocyclic cavity. The interactions via hydrogen bonding are responsible for high negative enthalpy and entropy changes accompanying the complexation of cyclodextrins with teriflunomide. These results were in agreement with the molecular modeling calculations, which provide a clearer picture of the involved interactions at the atomic level.     

Ligand-Installed Nanocarriers toward Precision Therapy

Development of drug-delivery systems that selectively target neoplastic cells has been a major goal of nanomedicine. One major strategy for achieving this milestone is to install ligands on the surface of nanocarriers to enhance delivery to target tissues, as well as to enhance internalization of nanocarriers by target cells, which improves accuracy, efficacy, and ultimately enhances patient outcomes. Herein, recent advances regarding the development of ligand-installed nanocarriers are introduced and the effect of their design on biological performance is discussed. Besides academic achievements, progress on ligand-installed nanocarriers in clinical trials is presented, along with the challenges faced by these formulations. Lastly, the future perspectives of ligand-installed nanocarriers are discussed, with particular emphasis on their potential for emerging precision therapies.     

Efficient GPU-based parallelization of solvation calculation for the blind docking problem

The Journal of Supercomputing - Molecular docking techniques are widely used in computational drug discovery. Most of these techniques simulate the way that a ligand interacts with a protein target...     

Bioactive compounds in wine: Resveratrol,hydroxytyrosol and melatonin: A review

Regular moderate wine consumption is often associated with reduced morbidity and mortality from a variety of chronic diseases in which inflammation is the root cause. This review is focused on three of the numerous bioactive compounds present in wine: resveratrol, hydroxytyrosol and melatonin. Resveratrol and hydroxytyrosol are polyphenols. Melatonin, recently described in wine, is an indoleamine. Their structures, concentrations in wine, bioavailability, pharmacokinetic and health promoting properties are reviewed. Resveratrol seems to be one of the most promising compounds due to its bioactivity, with wine being the main source of resveratrol in diet. Hydroxytyrosol, which its main source in diet is olive oil has been also found in both red and white wine in considerable amounts. Melatonin has been found in wine in low amounts. However, both high bioactivity and bioavailability have been attributed to it. They show antioxidant, cardioprotective, anticancer, antidiabetic, neuroprotective and antiaging activities. However, human studies are still in the initial stages and therefore further studies are needed.     

Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity,Halting Leukocyte Infiltration and Restoring Normal Metabolic Function

The increasing prevalence of inflammatory diseases and the adverse effects associated with the long-term use of current anti-inflammatory therapies prompt the identification of alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator of inflammation. Here, we show that apigenin has immune-regulatory activity in vivo. Apigenin conferred survival to mice treated with a lethal dose of Lipopolysaccharide (LPS) restoring normal cardiac function and heart mitochondrial Complex I activity. Despite the adverse effects associated with high levels of splenocyte apoptosis in septic models, apigenin had no effect on reducing cell death. However, we found that apigenin decreased LPS-induced apoptosis in lungs, infiltration of inflammatory cells and chemotactic factors’ accumulation, re-establishing normal lung architecture. Using NF-κB luciferase transgenic mice, we found that apigenin effectively modulated NF-κB activity in the lungs, suggesting the ability of dietary compounds to exert immune-regulatory activity in an organ-specific manner. Collectively, these findings provide novel insights into the underlying immune-regulatory mechanisms of dietary nutraceuticals in vivo.     

Effect of additive distribution in H2 absorption and desorption kinetics in MgH2 milled with NbH0.9 or NbF5

This paper presents a comparative study of H₂ absorption and desorption in MgH₂ milled with NbF₅ or NbH_0.9. The addition of NbF₅ or NbH_0.9 greatly improves hydriding and dehydriding kinetics. After 80 h of milling the mixture of MgH₂ with 7 mol.% of NbF₅ absorbs 60% of its hydrogen capacity at 250 °C in 30 s, whereas the mixture with 7 mol.% of NbH_0.9 takes up 48%, and MgH₂ milled without additive only absorbs 2%. At the same temperature, hydrogen desorption in the mixture with NbF₅ finishes in 10 min, whereas the mixture with NbH_0.9 only desorbs 50% of its hydrogen content, and MgH₂ without additive practically does not releases hydrogen. The kinetic improvement is attributed to NbH_0.9, a phase observed in the hydrogen cycled MgH₂ + NbF₅ and MgH₂ + NbH_0.9 materials, either hydrided or dehydrided. The better kinetic performance of the NbF₅-added material is attributed to the combination of smaller size and enhanced distribution of NbH_0.9 with more favorable microstructural characteristics. The addition of NbF₅ also produces the formation of Mg(H_xF_1-x)₂ solid solutions that limit the practically achievable hydrogen storage capacity of the material. These undesired effects are discussed.     

Conversion and hydroconversion of hydrocarbons on zeolite-based catalysts: an FT-IR study

The interaction of HZSM5 and Mo-ZSM5 with benzene, naphthalene, toluene, ortho-xylene, para-xylene, n-butane, isobutane, n-heptane, and methylcyclohexane, in the range 100–773 K has been investigated using FT-IR spectroscopy. Hydrogen bonded species with the internal bridging and the external terminal OHs has been detected. The reactivity at high temperature has also been studied. The access to the internal cavities and to the strongly acidic OHs is at least partly hindered in the case of Mo-ZSM5. The catalytic activity of ZSM5 was moderated by the addition of molybdenum, with lower cracking and higher liquid yields.     

Modelling diffusion and adsorption of As species in Fe/GAC adsorbent beds

BACKGROUND: Arsenic decontamination of drinking water by adsorption is a simple and robust operation. When designing packed bed adsorbers for arsenic, the main problems are the slow diffusion kinetics of As in microporous media and the lack of simple equations for predicting the performance of the equipment. Commercial iron‐doped granular activated carbon adsorbents (Fe/GAC) for groundwater arsenic abatement were studied in this work. Basic parameters for arsenate (As^V) adsorption were measured and their performance at larger scale was simulated with an approximate analytical model. RESULTS: In the 0–300 µg_As L^?1 range, the As^V adsorption isotherm on Fe/GAC was found to be approximately linear. Assuming Henry's law for adsorption and homogeneous surface diffusion with constant diffusivity for intrapellet mass transfer, an approximate model for flow and adsorption of arsenate inside packed bed adsorbers was developed, and reduced to an analytic compact solution using the quasi‐lognormal distribution (Q‐LND) approximation. The use of this model with fitted and reported parameters enabled the approximate simulation of industrial adsorbers and home point‐of‐use filters. Results show that industrial adsorbers meet the breakthrough condition with incomplete utilization of the adsorbent unless convenient process configurations are used. In point‐of‐use systems with short residence times intraparticle diffusion would drastically reduce the adsorbent performance. CONCLUSION: Assuming linear adsorption of As^V over Fe/GAC, an analytical approximate solution for flow and adsorption in packed beds can be obtained. The model seems to represent correctly the main features of industrial and home filters, however, more experimental data is necessary for scale‐up purposes. Copyright © 2011 Society of Chemical Industry