Fentanyl Structure as a Scaffold for Opioid/Non-Opioid Multitarget Analgesics

One of the strategies in the search for safe and effective analgesic drugs is the design of multitarget analgesics. Such compounds are intended to have high affinity and activity at more than one molecular target involved in pain modulation. In the present contribution we summarize the attempts in which fentanyl or its substructures were used as a μ-opioid receptor pharmacophoric fragment and a scaffold to which fragments related to non-opioid receptors were attached. The non-opioid ‘second’ targets included proteins as diverse as imidazoline I₂ binding sites, CB₁ cannabinoid receptor, NK₁ tachykinin receptor, D₂ dopamine receptor, cyclooxygenases, fatty acid amide hydrolase and monoacylglycerol lipase and σ₁ receptor. Reviewing the individual attempts, we outline the chemistry, the obtained pharmacological properties and structure-activity relationships. Finally, we discuss the possible directions for future work.     

SBA-15 mesoporous silica modified with rhodium by MDD method and its catalytic role for N<Subscript>2</Subscript>O decomposition reaction

SBA-15 mesoporous silicas modified with rhodium were studied as catalysts for the N₂O decomposition reaction. Rhodium was deposited on SBA-15 by the Molecular Designed Dispersion (MDD) method using Rh(acac)₃ as a precursor of active phase. The same method was used for the deposition of Cu, Fe, Al and Ti. The SBA-15 support modified with metals were characterized with respect to metal loading (EPMA), structure (XRD), texture (BET), morphology (SEM), Rh dispersion (oxygen chemisorption), surface acidity (pyridine adsorption) and chemical nature of introduced copper and iron species (UV–vis-DRS). The rhodium-containing SBA-15 samples were found to be active catalysts for the N₂O decomposition reaction. Deposition of Al on the Rh-loaded catalyst increased its activity. An opposite effect was observed for the samples modified with Cu and Fe.     

Modelling of mass loss of char particles during combustion in flow of inert material

The inspiration for this research was an attempt at the numerical simulation of the process of mass loss of char particles during its combustion in the upper zone of a CFB boiler furnace. In the first part of the research an experiment was carried out, during which singular char particles were burned in a flow of heated sand. During the course of this test manually polished spherical particles chosen from arbitrary real coal particles were used whose diameter amounted to 10 mm. The mass loss of burning particles was recorded with a tensometric branch scale. The measuring equipment applied enabled the observation of the mass loss both as a result of combustion and erosion resulting from the contact of inert material accelerated particles with the upper surface of the motionless particle being tested. The results of the experiment were compared with the results of numerical simulation, where for the first time the mass loss of a coal particle was presented as the superposition of two separate processes i.e. combustion and surface erosion. The values obtained indicated a good level of conformity which may illustrate the possibility of applying this model in real conditions.     

A method of concentration estimation of trienes,tetraenes, and pentaenes in evening primrose oil

There is no simple method available to estimate the concentration of conjugated fatty acids (CFA) with more than two double bonds in plant oils, because there are no commercially available complete sets of CFAs standards needed for such analysis. This paper presents such a method based on the absorption and fluorescence spectra of available CFAs standards and a computer program calculation. Using this method, the concentrations of the α‐eleostearic acid (conjugated trienoic acid (ELA) 8.8 × 10^?4 mol/L) and cis‐parinaric acid (conjugated tetraenoic acid (PnA) 3.5 × 10^?5 mol/L) in evening primrose oil were estimated. The accuracy of the calculation method is around 10%. Practical applications: This is the first report about the existence of CFAs in evening primrose oil. The described method estimates the total concentration of trienes, tetraenes, and pentaenes in evening primrose oils without using HPLC or other analytical methods. These CFAs are important from a health point of view. They are not synthesized by the human body. Therefore, plant oils containing these fatty acids (FA) are very valuable. Knowledge about the concentrations can be utilized to prepare a mixture of the plant oils with a favourable n‐3 to n‐6 FAs ratio and in addition containing CFAs.     

Coupling of N2O Decomposition and Ethylbenzene Dehydrogenation over γ-Al2O3-Supported Transition Metal Oxide Catalysts

Transition metal (Cr, Cu, Fe, Co and Ni) oxides supported on -alumina were characterized with respect to their textural parameters and reducibility and used as catalysts in decomposition of nitrous oxide and ethylbenzene (EB) dehydrogenation as well as coupling of both processes. High activity of -Al₂O₃ in N₂O decomposition coupled with EB dehydrogenation has been found. An increase in EB and N₂O conversion was observed when transition-metal-containing catalysts were used. The activity of catalysts depended on their reducibility. Maximum N₂O efficiency was observed for the Cr/-Al₂O₃ sample, whereas -Al₂O₃-supported Cu and Fe oxide systems showed about 50% efficiency of N₂O in the reaction. An influence of the molar ratio of N₂O/EB on activity and selectivity of the catalysts was found. An excess of N₂O resulted in an increase in CO₂ formation at nearly constant styrene yield.     

Rhodium(I) complex catalyst immobilized on terpolymers of N‐vinylpyrrolidinone and 1‐vinylimidazole

The hydrosilylation of cyclohexanone and acetone with triethysilane and diphenysilane catalyzed by polymer‐supported Rh(I) complex has been investigated. Two terpolymers of styrene, divinylbenzene, and 1‐vinylimidazole (S/DVB/VI) or N‐vinylpyrrolidinone (S/DVB/NVP) were used as the catalysts supports. Physical characterization of these materials has involved the measurements of the structural parameters in the dry and swollen states by DSC, the nitrogen BET adsorption method and inverse steric exclusion chromatography ISEC. From these results it can be concluded that the original polymer structure has been changed during the complex attachment giving rise to materials of higher porosity. X‐ray photoelectron spectroscopy XPS, IR, and AAS spectroscopy were used to characterization of heterogeneous complexes before and after use. The effect of the morphology of the support on the catalytic properties of the polymer‐supported Rh(I) species was tested in the hydrosilylation of ketones and correlated with the reaction mechanism. It was demonstrated that the high selectivity of homogeneous rhodium complex toward the silyl ethers can be partially reversed to the dehydrogenative silylation products by a proper choice of polymer support with favorable microporous structure. Recycling tests demonstrated high stability of the supported catalysts during prolonged use. The constant selectivity of the supported catalysts demonstrated during recycling experiments showed that they could be useful for practical application. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity

Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases.     

A Stochastic Petri Net-Based Model of the Involvement of Interleukin 18 in Atherosclerosis

Interleukin 18 (IL-18) is a proinflammatory and proatherogenic cytokine with pleiotropic properties, which is involved in T and NK cell maturation and the synthesis of other inflammatory cytokines and cell adhesion molecules. It plays a significant role in orchestrating the cytokine cascade, accelerates atherosclerosis and influences plaque vulnerability. To investigate the influence of IL-18 cytokine on atherosclerosis development, a stochastic Petri net model was built and then analyzed. First, MCT-sets and t-clusters were generated, then knockout and simulation-based analysis was conducted. The application of systems approach that was used in this research enabled an in-depth analysis of the studied phenomenon. Our results gave us better insight into the studied phenomenon and allow revealing that activation of macrophages by the classical pathway and IL-18-MyD88 signaling axis is crucial for the modeled process.