Discovery of New Antiproliferative Imidazopyrazole Acylhydrazones Able To Interact with Microtubule Systems

Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC₅₀ values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here.     

Microbiological shelf life and sensory evaluation of fruit juices treated by high-intensity pulsed electric fields and antimicrobials

The effect of combining high-intensity pulsed electric fields (HIPEF) with citric acid or cinnamon bark oil, as antimicrobial substances, on the microbiological shelf life of strawberry, orange, apple, pear and tomato juices was evaluated in addition to the sensory properties of these products. An extension of the microbiological shelf life of fruit juices treated by HIPEF with or without antimicrobial substances was observed in comparison with those juices without processing. Naturally occurring microorganisms in the juices were inactivated by HIPEF treatment. Among the HIPEF treated juices, those from strawberry and orange did not show microbial growth along the 91 days of storage at 5 °C. However, resident microbial populations in apple, pear and tomato juices only were controlled during that time when HIPEF was combined with antimicrobials. Therefore, combinations of those treatments may be a feasible alternative to thermal pasteurization to ensure the microbiological quality and safety in juices, and to avoid the risk of foodborne illness caused by the consumption of these commodities. No significant changes on the sensory attributes in all studied fruit juices processed by HIPEF were found; but, when citric acid or cinnamon bark oil were added, noticeable changes on some sensory attributes such as aroma, taste and sourness of these fruit juices were perceived.     

Operando Raman–GC studies of alumina-supported Sb-V-O catalysts and role of the preparation method

The interactions between Sb and V are studied by operando Raman–GC methodology during propane ammoxidation in order to understand the effect of the preparation method and reaction conditions on the structure and activity/selectivity of alumina-supported Sb-V-O catalysts. Dispersed V(V) species react with antimony species during propane ammoxidation to form VSbO₄; partially reversible transformations towards surface vanadium (V) species may account for the catalytic redox cycle. The catalytic performance is determined by the interaction between Sb and V, which is affected by the preparation method and the reaction conditions.     

Role of Plant Volatiles in Host Plant Recognition by <Emphasis Type="Italic">Listronotus maculicollis</Emphasis> (Coleoptera: Curculionidae)

The annual bluegrass weevil (ABW), Listronotus maculicollis Kirby, is an economically important pest of short cut turfgrass. Annual bluegrass, Poa annua L., is the most preferred and suitable host for ABW oviposition, larval survival and development. We investigated the involvement of grass volatiles in ABW host plant preference under laboratory and field conditions. First, ovipositional and feeding preferences of ABW adults were studied in a sensory deprivation experiment. Clear evidence of involvement of olfaction in host recognition by ABW was demonstrated. Poa annua was preferred for oviposition over three bentgrasses, Agrostis spp., but weevils with blocked antennae did not exhibit significant preferences. ABW behavioral responses to volatiles emitted by Agrostis spp. and P. annua were examined in Y-tube olfactometer assays. Poa annua was attractive to ABW females and preferred to Agrostis spp. cultivars in Y-tube assays. Headspace volatiles emitted by P. annua and four cultivars of Agrostis stolonifera L. and two each of A. capillaris L. and A. canina L. were extracted, identified and compared. No P. annua specific volatiles were found, but Agrostis spp. tended to have larger quantities of terpenoids than P. annua. (Z)-3-hexenyl acetate, phenyl ethyl alcohol and their combination were the most attractive compounds to ABW females in laboratory Y-tube assays. The combination of these compounds as a trap bait in field experiments attracted adults during the spring migration, but was ineffective once the adults were on the short-mown turfgrass. Hence, their usefulness for monitoring weevil populations needs further investigation.     

Complex modification effect of linseed cake as an agricultural waste filler used in high density polyethylene composites

Linseed cake (LC) is a by-product of agricultural industry which does not have any large-scale industrial applications. The possibilities of its utilization as filler with plasticizing ability for high density polyethylene (HDPE)-based composites have been investigated. Composites containing 5, 10, 20 and 30 wt% of the waste filler have been prepared using a melt mixing method. The influence of the LC on the mechanical and thermomechanical properties of the composites, as well as their water absorption and morphology, have been evaluated by the following methods: static tensile test, impact strength assessment using Dynstat method, hardness measurements, differential scanning calorimetry, dynamic mechanical thermal analysis, scanning electron microscopy observations, measurements of Vicat’s softening temperature and water uptake test. Application of different measuring techniques allows for describing complex modification effects of the composites’ properties changes induced by the presence of lignocellulosic filler with high oil content. The results of the study proved a pronounced influence of LC on high density polyethylene-based composites, especially a plasticizing effect of crude linseed oil contained by the waste filler particles. LC also has been assumed to affect the polymeric matrix crystallization process. It was found that complex modification of polyethylene results from simultaneously occurring different phenomena including: plasticization of the HDPE by linseed oil, improved crystallinity of the semicrystalline matrix, presence of the rigid lignocellulosic particles dispersed in polymer and accumulation of the oil in the interfacial regions.     

Morphology and adsorption properties of chemically modified MWCNT probed by nitrogen,n-propane and water vapor

The poor compatibility of carbon materials with different dispersion media can be overcome by surface functionalization. In this work, multiwall carbon nanotubes (MWCNTs) were doped by oxygen and nitrogen at low concentrations. Morphological and structural changes caused by chemical treatment were monitored using nitrogen, propane and water vapor adsorption measurements. Pore size distribution (PSD) functions derived from various models are compared. The contribution of slit-shaped pores to the total surface area available for adsorbed molecules is smaller than that of cylindrical pores. Functionalities with heteroatoms (both O and N) enhance water adsorption onto MWCNTs. However, no statistical difference is observed between the water adsorption properties of O- or N-containing MWCNTs.     

Noble metal ion sorption by pyridyl and bipyridyl group‐containing chelating polymers

A series of eighteen 4‐vinylpyridine and 4‐methyl‐4′‐vinylbipyridine copolymers with different crosslinkers was examined as sorbents for the noble metal ions of Ag(I), Au(III), Pd(II), and Pt(II) from aqueous solutions. The chelating polymers possess appreciable sorption selectivity for Au(III) over Ag(I) and for Pd(II) over Pt(II). Binding abilities of the copolymers toward the noble metal ions vary as the identity of the chelating heterocyclic amine moiety and the structure of the crosslinkers are altered. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 207–213, 2001     

Protein-ion Interactions: Simulations of Bovine Serum Albumin in Physiological Solutions of NaCl,KCl and LiCl

Specific interactions that depend on the nature of electrolytes are observed when proteins and other molecules are studied by potentiometric, spectroscopic and theoretical methods at high salt concentrations. More recently, it became clear that such interactions may also be observed in solutions that can be described by the Debye-Hückel theory, i.e., at physiological (0.1 mol dm⁻³) and lower concentrations. We carried out molecular dynamics simulations of bovine serum albumin in physiological solutions at T=300 and 350 K. Analysis of the simulations revealed some differences between LiCl solutions and those of NaCl and KCl. The binding of Li⁺ ions to the protein was associated with a negative free energy of interaction whereas much fewer Na⁺ and K⁺ ions were associated with the protein surface. Interestingly, unlike other proteins BSA does not show a preference to Na⁺ over K⁺. Quantum chemical calculations identified a significant contribution from polarisation to the hydration of Li⁺ and (to a lesser degree) Na⁺, which may indicate that polarisable force-fields will provide more accurate results for such systems.     

The Composition of Mixed Micelles Formed by Dodecyl Trimethyl Ammonium Bromide and Benzethonium Chloride in Water

The composition of the mixed micelles formed by benzethonium chloride and dodecyl trimethyl ammonium bromide in water were experimentally determined by a combination of surfactant ion-selective electrodes and UV–Vis spectroscopy measurements. Results were compared with the computed compositions from three theories on mixed micelles available in the literature (Regular Solution, Motomura’ and Georgiev’s). The basis of the Junquera and Aicart method and the determination of the micelle aggregation number (N) by pyrene fluorescence quenching, i.e., the constancy of N and the mixed micelle composition when the total concentration is changed, were not supported by our experimental results. Experimental micelle compositions were statistically equal to those computed by Regular Solution Theory. The mixed micelle composition and the quantity of non-micellized surfactant molecules change with concentration above the critical micelle concentration, and therefore do not support the assumptions used in the Junquera and Aicart procedure and in the determination of N by pyrene fluorescence quenching. The reason why the latter procedure gives N values similar to those obtained from other techniques is discussed.     

One‐pot synthesis of {Mo6I8}4+‐doped polystyrene microspheres via a free radical dispersion copolymerisation reaction

Molybdenum octahedral clusters, when incorporated into an appropriate polymer matrix, are considered as promising agents for a range of biological applications. This work describes the one‐pot synthesis, morphology and cellular toxicity of nano‐sized polystyrene beads doped with luminescent cluster complexes [{Mo₆X₈}(NO₃)₆]^2? (X = Cl, Br or I). Specifically, the particles were obtained by free radical dispersion copolymerisation of styrene and methacrylic acid or 4‐vinylpyridine in the presence of the cluster complexes. The effects of the cluster loading in the reaction mixture on both the content of the final material and number‐average molar mass of the copolymers were evaluated. © 2017 Society of Chemical Industry