Antiplatelet Effect and Selective Binding to Cyclooxygenase (COX) by Molecular Docking Analysis of Flavonoids and Lignans

The known flavonoids ginkgetin (1), taiwanhomoflavone A (2), taiwanhomoflavone B (3), and taiwanhomoflavone C (4) and eight known lignans: justicidin B (9), justicidin C (10), justicidin D (11), chinensinaphthol methyl ether (12), procumphthalide A (13), procumbenoside A (15), and ciliatosides A (16) and B (17) were isolated from Cephalotaxus wilsoniana and Justicia species, respectively. The antiplatelet effects of the above constituents on human platelet-rich plasma (PRP) were evaluated. Of the compounds tested on human PRP, compounds 1, 4, 9, and 11 showed inhibition of secondary aggregation induced by adrenaline. Compound 1 had an inhibitory effect on cyclooxygenase-1 (COX-1). Molecular docking studies revealed that 1 and the related compounds apigenin (5), cycloheterophyllin (6), broussoflavone F (7), and quercetin (8) were docked near the gate of active site of COX-1. It indicated that the antiplatelet effect of 1, 4, 9, and 11 is partially owed to suppression of COX-1 activity and reduced thromboxane formation. Flavonoids, 1, 5, 6, 7, and 8 may block the gate of the active site of COX-1 and interfere the conversion of arachidonic acid to prostaglandin (PG) H₂ in the COX-1 active site.     

Interpolymer complexes of poly(acrylamide) and poly(N-isopropylacrylamide) with poly(acrylic acid): a comparative study

The interpolymer complexation, through successive hydrogen bonding, between poly(acrylamide) (PAAm) and poly(N-isopropylacrylamide) (PNiPAAm) with poly(acrylic acid) (PAA) in aqueous solution has been viscometrically and potentiometrically investigated. The stoichiometry of the complexes formed was determined. By comparing the strength of the two complexes the very important contribution of the hydrophobic interaction in their formation has been indicated.     

Protease inhibitors and in vitro digestibility of karanja (Pongamia glabra) oil seed residue. A comparative study of various treatments

Trypsin and chymotrypsin inhibitor activities (TIA and CIA) were assayed before and after processing of Karanja oil seed residue. Upon treatment, the loss of TIA and CIA varied with the type of processing or extraction: the reduction after solvent extraction ranged between 34 and 15%, respectively. These activities were completely removed in 2.4% HCl; 83.35 and 54.86% were removed on autoclaving; 33.86 and 15.30% on fermentation; and removal was 4.36–83.69% and 3.66–77.59% after exposure to different doses of gamma radiation (1, 5, 10, and 50 KGy). An in vitro digestibility study was carried out to confirm the inactivation of the inhibitors and showed improvements from 45 to 81%, with the maximum observed in 2.4% HCl solvent-refluxed residue. A linear relationship was observed between the reduction in protease inhibitor activities and the improvement in digestibility.     

2‐Carbaborane‐3‐phenyl‐1H‐indoles—Synthesis via McMurry Reaction and Cyclooxygenase (COX) Inhibition Activity

Cyclooxygenase‐2 (COX‐2) inhibitors have been the focus of medicinal chemistry efforts for years, and many compounds that exhibit high selectivity and affinity have been developed. As carbaboranes represent interesting pharmacophores as phenyl mimetics in drug development, this paper presents the synthesis of carbaboranyl derivatives of COX‐2‐selective 2,3‐disubstituted indoles. Despite the lability of carbaboranes under reducing conditions, 2‐carbaborane‐3‐phenyl‐1H‐indoles could be synthesized by McMurry cyclization of the corresponding amides. Whereas the meta‐carbaboranyl‐substituted derivatives lacked COX inhibitory activity, an ortho‐carbaboranyl analogue was active, but showed a selectivity shift toward COX‐1.     

Blends of poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) with polystyrene-based thermoplastic rubbers: A comparative study

This work presents the first part of our study on the modification of poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) with styrenic thermoplastic rubbers. Polystyrene-b-polyisobutylene-b-polystyrene (SIBS), polystyrene-b-polybutadiene-b-polystyrene (SBS) and polystyrene-b-poly(ethylene/butylene)-b-polystyrene (SEBS) triblock copolymers were melt blended with PPO and the blends were characterized. Differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and transmission electron microscopic (TEM) studies revealed that PPO/SEBS blends displayed the most pronounced phase-separated morphology with largest rubbery domains. SBS showed the most miscibility, and the least detrimental effect on dynamic mechanical properties and tensile strength. The results of this comparative study guided us to develop optimum conditions for the impact modification of PPO by SIBS thermoplastic rubbers.     

Corrosion inhibitors part V: QSAR of benzimidazole and 2-substituted derivatives as corrosion inhibitors by using the quantum chemical parameters

Quantum chemical SCF calculations of some parameters of benzimidazoles were correlated with their inhibition efficiency in case of steel in aqueous acidic medium. Geometric structures, total negative charge on the molecule (TNC), highest occupied molecular orbital (E_HOMO), lowest unoccupied molecular orbital (E_LUMO), dipole moment (μ) and linear solvation energy terms, molecular volume (Vi) and dipolar-polarization (π*) were correlated to corrosion inhibition efficiency. The correlation between quantum parameters obtained by AM1 calculation and experimental inhibition efficiency has been validated by single point calculations for the semi-empirical AM1 structure using B3LYP/6-31G* as a higher level of theory. Equations were proposed using linear regression analysis to calculate corrosion inhibition efficiency. It was established that the increase of the orbital energies E_HOMO favors the inhibition efficiency toward steel corrosion. The proposed linear equations were applied to predict the corrosion inhibition efficiency of some related structures in order to select molecules of possible activity from a library compounds.     

Cellulose biosynthesis inhibitors: comparative effect on bean cell cultures

The variety of bioassays developed to evaluate different inhibition responses for cellulose biosynthesis inhibitors makes it difficult to compare the results obtained. This work aims (i) to test a single inhibitory assay for comparing active concentrations of a set of putative cellulose biosynthesis inhibitors and (ii) to characterize their effect on cell wall polysaccharides biosynthesis following a short-term exposure. For the first aim, dose-response curves for inhibition of dry-weight increase following a 30 days exposure of bean callus-cultured cells to these inhibitors were obtained. The compound concentration capable of inhibiting dry weight increase by 50% compared to control (I(50)) ranged from subnanomolar (CGA 325'615) to nanomolar (AE F150944, flupoxam, triazofenamide and oxaziclomefone) and micromolar (dichlobenil, quinclorac and compound 1) concentrations. In order to gain a better understanding of the effect of the putative inhibitors on cell wall polysaccharides biosynthesis, the [(14)C]glucose incorporation into cell wall fractions was determined after a 20 h exposure of cell suspensions to each inhibitor at their I(50) value. All the inhibitors tested decreased glucose incorporation into cellulose with the exception of quinclorac, which increased it. In some herbicide treatments, reduction in the incorporation into cellulose was accompanied by an increase in the incorporation into other fractions. In order to appreciate the effect of the inhibitors on cell wall partitioning, a cluster and Principal Component Analysis (PCA) based on the relative contribution of [(14)C]glucose incorporation into the different cell wall fractions were performed, and three groups of compounds were identified. The first group included quinclorac, which increased glucose incorporation into cellulose; the second group consisted of compound 1, CGA 325'615, oxaziclomefone and AE F150944, which decreased the relative glucose incorporation into cellulose but increased it into tightly-bound cellulose fractions; and the third group, comprising flupoxam, triazofenamide and dichlobenil, decreased the relative glucose incorporation into cellulose and increased it into a pectin rich fraction.     

Crystallization,rheological behavior and mechanical properties of poly(vinylidene fluoride) composites containing graphitic fillers: a comparative study

The effect of three kinds of graphitic fillers with distinct morphologies, natural graphite sheets (NGs), chemically reduced graphite oxide sheets (CRGs) and thermally reduced graphite oxide sheets (TRGs), on the crystallization, rheological behavior and mechanical properties of poly(vinylidene fluoride) (PVDF)‐based composites has been investigated comparatively. NGs exhibit smooth surface and multilayer‐stacked structure; most CRGs are in the form of aggregates that are restacked during reduction; while TRGs show a wrinkled topography of relatively thin graphene sheets. The introduction of these graphitic fillers into the PVDF matrix contributes differently to the crystallization, rheological behavior and mechanical properties of the composites. Among them, TRGs show the greatest strengthening effect, as revealed by rheological and dynamic mechanical responses. Compared with chemical reduction technology, thermal reduction is a more economical, environmentally friendly and scalable approach to prepare functionalized graphene sheets. Copyright © 2012 Society of Chemical Industry     

Adsorption behavior of U(VI)/Th(IV) by acid-leached red mud: A comparative study

Acid-leached red mud, a type of inorganic-adsorptive by-product of bauxite Bayer process via acid leaching, was used for the removal of U(VI)/Th(IV) from aqueous solutions. Variables of the adsorption such as contact time, temperature, solution pH, initial concentration and dose of acid-leached red mud were investigated. The results indicated that the adsorption is strongly affected by dosage, the solution pH, contact time and initial concentration. The isothermal data were fitted with both Langmuir and Freundlich equations, but the data fitted the former better than the latter. A pseudo-first-order kinetic model and pseudo-second-order kinetic model were used to describe the kinetic data, but the pseudo-second-order kinetic model was the better. Thermodynamic parameters such as enthalpy (ΔH ^○ ), entropy (ΔS ^○ ) and free energy change (ΔG ^○ ) were calculated, and the negative ΔG ^○ values of U(VI)/Th(IV) at different temperatures confirmed the adsorption processes were spontaneous.     

A comparative study of the exocrine products of cleptoparasitic bees (Holcopasites) and their hosts (Calliopsis) (Hymenoptera: Anthophoridae,Andrenidae)

The cephalic secretion of females of the cleptoparasitic beeHolcopasites calliopsidis contains two main volatiles, 6-methyl-5-hepten-2-one and geranyl acetone. The mandibular gland secretion of its host,Calliopsis andreniformis, on the other hand, contains the two isomeric forms of citral (neral and geranial). Neral and geranial are also produced by mandibular glands of two other species ofCalliopsis and one species in the related genusNomadopsis. The Dufour's gland ofC. andreniformis contains an oily secretion composed of hydrocarbons that are deposited on the brood cell walls and pollen balls providing a waterproof lining for both.     

Resistance of pure and mixed rare earth silicates against calcium-magnesium-aluminosilicate (CMAS): A comparative study

Rare earth silicate environmental barrier coatings (EBCs) are state of the art for protecting SiC ceramic matrix composites (CMCs) against corrosive media. The interaction of four pure rare earth silicate EBC materials Yb₂SiO₅, Yb₂Si₂O₇, Y₂SiO₅, Y₂Si₂O₇ and three ytterbium silicate mixtures with molten calcium-magnesium-aluminosilicate (CMAS) were studied at high temperature (1400°C). The samples were characterized by SEM and XRD in order to evaluate the recession of the different materials after a reaction time of 8 hours. Additionally, the coefficient of thermal expansion (CTE) was determined to evaluate the suitability of Yb silicate mixtures as EBC materials for SiC CMCs. Results show that monosilicates exhibit a lower recession in contact with CMAS than their disilicate counterparts. The recession of the ytterbium silicates is far lower than the recession of the yttrium silicates under CMAS attack. Investigation of the ytterbium silicate mixtures exposes their superior resistance to CMAS, which is even higher than the resistance of the pure monosilicate. Also their decreased CTE suggests they will display better performance than the pure monosilicate.     

ATRP poly(acrylate) star formation: A comparative study between MALDI and ESI mass spectrometry

Optimised matrix-assisted laser desorption/ionisation (MALDI) and electrospray ionisation (ESI) mass spectrometry (MS) methodologies were systematically compared in terms of their relative abilities to identify distinct chemical species present in samples associated with a polymer mechanistic study. In order to perform the investigation, formation processes involved in atom transfer radical polymerisation (ATRP) mediated methyl acrylate (MA) star polymerisations were studied. In addition to the 4-armed ATRP initiator employed in the polymerisations, initiator side-products were found to generate oligomeric chains. At a relatively high monomer to polymer conversion, terminal Br loss was observed in these oligomers; this Br loss was hypothesised to occur via degradative transfer reactions involving the radicals (CH₃)₂?OH, ?H₃ and ?H₂COCH₃, which were derived from the acetone used as a solvent in the polymerisations, as well as hydrogen radicals donated by the ligand N,N′,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA). In performing these studies, ESI was found to identify a greater number of distinct chemical species in the samples under investigation when compared to the employed MALDI technique, suggesting that the utilisation of ESI must be strongly considered in polymer mechanistic investigations if the maximum number of end-group functionalities within a given polymer sample are to be identified.     

A comparative study of ethylene polymerization by bis(aminotropone) Ti catalysts

A series of titanium aminotropone complexes bearing a pair of chelating [O–N] ligands have been synthesized and used for polymerization of ethylene successfully. Ethylene polymerization reactions were carried out at different conditions using the prepared catalysts. The activities for ethylene polymerization were significantly dependent on the catalyst structure. The polymerization activity increased with increasing of the both monomer pressure and [MAO]:[Ti] ratio. The highest activity of the catalysts was obtained at about 30–40 °C. It was demonstrated that unlike the high performance Ti–FI catalysts, bis(aminotropone) Ti catalysts do not require the presence of steric bulk in close proximity to the oxygen moiety. Introduction of the bulky alkyl substitution next to the oxygen moiety decreased the activity of the catalysts. Density Functional Theory (DFT) studies reveal that the active species derived from these catalysts normally possess higher electrophilicity nature compared with those produced using bis(phenoxy-imine) Ti catalysts (Ti–FI catalysts). Hydrogen was used as the chain transfer agent. The activities of the catalysts were increased with hydrogen concentration to some extent, but the M _v values of the obtained polymers were decreased. Crystallinity and melting point of the obtained polymer were between 42–62% and 102–124 °C, respectively. Higher pressure increased both the crystallinity and the M _v values of the resulting polymers. The catalyst 8a also produced PE with almost narrow polydispersities (1.10–2.55) as is typical for single-site catalysts. However, PDI was broadened by time.     

3D QSAR pharmacophore modeling, in silico screening, and density functional theory (DFT) approaches for identification of human chymase inhibitors

Human chymase is a very important target for the treatment of cardiovascular diseases. Using a series of theoretical methods like pharmacophore modeling, database screening, molecular docking and Density Functional Theory (DFT) calculations, an investigation for identification of novel chymase inhibitors, and to specify the key factors crucial for the binding and interaction between chymase and inhibitors is performed. A highly correlating (r = 0.942) pharmacophore model (Hypo1) with two hydrogen bond acceptors, and three hydrophobic aromatic features is generated. After successfully validating "Hypo1", it is further applied in database screening. Hit compounds are subjected to various drug-like filtrations and molecular docking studies. Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with key active site amino acids are identified as potent chymase hits. Moreover, DFT study is performed which confirms very clear trends between electronic properties and inhibitory activity (IC(50)) data thus successfully validating "Hypo1" by DFT method. Therefore, this research exertion can be helpful in the development of new potent hits for chymase. In addition, the combinational use of docking, orbital energies and molecular electrostatic potential analysis is also demonstrated as a good endeavor to gain an insight into the interaction between chymase and inhibitors.     

A comparative study of nanocomposites based on a recycled poly(methyl methacrylate) matrix containing several nanoclays

Nanocomposites of recycled poly(methyl methacrylate) (PMMA) and both natural (Nanomer PGV MMT), and organically modified Nanomer I44P, Nanomer I30P and Cloisite 30B montmorillonites (O‐MMT) were prepared by solution dispersion method with the use of two miscible solvents, followed by melt intercalation process in a twin‐screw miniextruder. The final product has been found to show a homogeneous structure with a uniform dispersion/intercalation of the silicate layers. The effect of MMT and O‐MMT layers on the properties of the nanocomposites was investigated and characterized by UV–vis spectroscopy, differential scanning calorimetry, atomic force microscopy, and mechanical testing. Higher contents of nanoclay in nanocomposites exhibited worse light transmittance capacity but higher tensile modulus. Properties of the samples depended not only on the clay contents (up to 10 wt%) but also on the clay type employed. POLYM. COMPOS., 2008. © 2008 Society of Plastics Engineers     

Quantitative Structure-Activity Relationship (QSAR) Studies on the Toxic Effects of Nitroaromatic Compounds (NACs): A Systematic Review

Nitroaromatic compounds (NACs) are ubiquitous in the environment due to their extensive industrial applications. The recalcitrance of NACs causes their arduous degradation, subsequently bringing about potential threats to human health and environmental safety. The problem of how to effectively predict the toxicity of NACs has drawn public concern over time. Quantitative structure–activity relationship (QSAR) is introduced as a cost-effective tool to quantitatively predict the toxicity of toxicants. Both OECD (Organization for Economic Co-operation and Development) and REACH (Registration, Evaluation and Authorization of Chemicals) legislation have promoted the use of QSAR as it can significantly reduce living animal testing. Although numerous QSAR studies have been conducted to evaluate the toxicity of NACs, systematic reviews related to the QSAR modeling of NACs toxicity are less reported. The purpose of this review is to provide a thorough summary of recent QSAR studies on the toxic effects of NACs according to the corresponding classes of toxic response endpoints.