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Selective reductions of semicyclic imides either to hemiaminals ( endo carbonyl reduction) or to aldehydes and amines ( exo carbonyl reduction) in high yields by Schwartz's reagent (Cp2ZrHCl) are reported. Mechanistic aspects of these reactions have been investigated at the DFT ab initio level with consideration of implicit solvent effects and thermal and pressure corrections to 298 K/1 atm. The reactions proceed from the reagents to very stable final Zr-oxo intermediates through the formation of σ complexes and subsequent four-center transition state structures (1,2-migratory insertion). The energetic barriers for the insertion steps depend strongly on the natures of the ancillary groups at the reducing carbonyl groups. N-Carbamoyl groups are reduced to hemiaminals whereas N-acyl groups react at the exo carbonyl groups. The absence of the second carbonyl group in the simple N-methyl-2-pyrrolidone (less oxidized system) strongly reduces the thermodynamic drive for the formation of the metallocene oxo intermediate and allows an explanation of the remarkable chemoselectivity of the hydrozirconation. The zirconocene-oxo intermediates hydrolyze quickly throughout an ionic mechanism in which water molecules strongly assist the process by stabilizing ion pair separation. The computational results are consistent with a large set of experimental data on reduction of γ-lactam and isoxazolidinone derivatives under mild conditions. They provide a way to explain and predict the relative importance of the two competitive endo/ exo reduction channels of semicyclic imides by considering the electronic and steric features of substituents. [ABSTRACT FROM AUTHOR]

Two series of novel dumbbell-shaped polyhedral oligomeric silsesquioxanes (POSSs), fully functionalized with phenyl groups at the corner of the silicon cages, were used to prepare polystyrene (PS) nanocomposites through the method of in situ polymerization. The percentage of the molecular filler reinforcement was set as 5% w/w of POSS and was checked by 1H-NMR spectroscopy. The obtained nanocomposites were characterized by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Thermal and morphological properties were evaluated and compared among the nanocomposites obtained using the two different series of dumbbell-shaped POSSs and with the net PS. The thermal parameters for the prepared nanocomposites were very high when compared with those of neat PS, and they evidenced significant differences when an aliphatic or aromatic bridge was used to link the silicon cages. SEM analysis results allow us to hypothesize a justification for the different resistance to thermal degradation showed by the two series of molecular reinforcement. [ABSTRACT FROM AUTHOR]

Abstract: Arenediyne–isoxazolidine conjugates have been synthesized as a new scaffold for the development of bioactive mimics. Some of the synthesized compounds are endowed with antiproliferative activity against three human cancer cell lines. Their thermal reactivity suggests that the biological activity probably could not be linked to the Bergman cyclization. [Copyright &y& Elsevier]

Purpose: To compare the efficacy of a personal dietary intervention on gestational weight gain control with a general intervention promoting healthy eating. Methods: Prospective, controlled study including 154 low-risk pregnant women randomly allocated to two groups: 77 receiving a personalized diet plan and a close follow-up by a dietician (intervention group), 77 receiving standard dietary care by means of a brochure on healthy eating during pregnancy (control group). Pre-pregnancy weight, gestational age, height, weight and BMI at baseline, weight at term, gestational age at delivery and newborn weight were recorded for all participants. The primary end-point was the difference in body weight between baseline and term. Secondary end-points were the difference in body weight between pre-pregnancy and term and in newborn weights. Results: Maternal weight gain at term was significantly lower both as compared to pre-pregnancy weight (8.2 ± 4.0 vs. 13.4 ± 4.2 kg; p < 0.001) and to weight at baseline (7.7 ± 3.8 vs. 13.7 ± 4.3 kg; p < 0.001) in the intervention group as compared to controls. A positive, significant correlation between the delta weight between baseline and term and newborn weight was observed in both groups, but stronger in patients from the intervention group (intervention group R = 0.76, p < 0.001; control group R = 0.35, p = 0.01). Conclusions: This study suggests that a personalized nutritional intervention, in which the dietician plays an active role within the obstetric team, may represent a successful approach in limiting weight gain in pregnant women. [ABSTRACT FROM AUTHOR]

Abstract: A synthetic approach towards a series of 3-hydroxymethyl-5-(1H-1,2,3-triazol)isoxazolidines has been reported, according to a procedure based on the cycloaddition reaction, under microwave irradiation, of a nitrone with 1-vinyl triazoles, prepared by a click reaction of azides with alkynes. Biological tests show that the synthesized compounds are able to inhibit proliferation of follicular and anaplastic human thyroid cancer cell lines, with IC50 values ranging from 3.87 to 8.76μM. The obtained compounds induce caspase-3 activation and DNA fragmentation prevalently in follicular human thyroid cancer cell lines. [Copyright &y& Elsevier]

Abstract: A series of modified N,O-nucleosides, characterized by the presence of a furopyrimidine moiety, has been synthesized by exploiting a Sonogashira cross coupling reaction of 1-isoxazolidinyl-5-iodouracil with alkynes, followed by treatment with CuI in refluxing TEA/MeOH mixture. The obtained compounds were screened against both RNA and DNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations. However, some of them were able to inhibit proliferation of MRC-5, Vero, BS-C-1 cells by 50% (CC50) at concentrations ranging from 0.7 to 62.5mM. [Copyright &y& Elsevier]

Abstract: The effects of an extract from Citrus bergamia (BSext) and those of two products purified from the same extract, that is, nomilin and limonin, and reference compounds, towards HTLV-1 have been reported. Moreover, they were also compared with those obtained towards HIV-1. Results showed that the efficacy of both BSext and limonin in inhibiting HTLV-1 as well as HIV-1 expression in infected cells, as evaluated by comparable quantitative assays, was close to that of the effective, reference compounds, respectively. The protective effect of BSext and of the purified products was associated with the inhibition of both HTLV-1 and HIV-1 RT activities in conceptually similar, cell-free assays. The cytotoxicity of the assayed compounds of natural origin was substantially less pronounced than that of the reference compounds, thus showing a favourable selectivity index for the novel BSext product. [Copyright &y& Elsevier]

Abstract: Phosphonated isoxazolinyl nucleosides have been prepared via 1,3-dipolar cycloaddition reaction of nitrile oxides with corresponding vinyl or allyl nucleobases for antiviral studies. The cytotoxicity, the anti-HSV activity and the RT-inhibitory activity of the obtained compounds were evaluated and compared with those of AZT and diethyl{(1′SR,4′RS)-1′-[[(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)]-3′-methyl-2′-oxa-3′-azacyclopent-4′-yl]}methylphosphonate, a saturated phosphonated dihydroisoxazole nucleoside analogue. [Copyright &y& Elsevier]

A straightforward approach to new polycyclic heterocycles, 1H-benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-ones, is presented. It is based on the ZnCl2-promoted deprotective 6-endo-dig heterocyclization of N-Boc-2-alkynylbenzimidazoles under mild conditions (CH2Cl2, 40 °C for 3 h). The zinc center plays a dual role, as it promotes Boc deprotection (with formation of the tert-butyl carbocation, which can be trapped by substrates bearing a nucleophilic group) and activates the triple bond toward intramolecular nucleophilic attack by the carbamate group. The structure of representative products has been confirmed by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Three new chiral Mn macrocycle catalysts containing 20 or 40 atoms in the macrocycle were synthetized and tested in the enantioselective epoxidation of cis-β-ethyl-styrene and 1,2-dihydronathalene. The effect of the presence of a binaphtol (BINOL) compound in the catalyst backbone has been evaluated, including by Density Functional Theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

Herein, we assessed the effect of full native peptide of amyloid-beta (Aβ) (1-42) and its fragments (25-35 and 35-25) on tissue transglutaminase (TG2) and its isoforms (TG2-Long and TG2-Short) expression levels on olfactory ensheathing cells (OECs). Vimentin and glial fibrillary acid protein (GFAP) were also studied. The effect of the pre-treatment with indicaxanthin from Opuntia ficus-indica fruit on TG2 expression levels and its isoforms, cell viability, total reactive oxygen species (ROS), superoxide anion (O2−), and apoptotic pathway activation was assessed. The levels of Nestin and cyclin D1 were also evaluated. Our findings highlight that OECs exposure to Aβ(1-42) and its fragments induced an increase in TG2 expression levels and a different expression pattern of its isoforms. Indicaxanthin pre-treatment reduced TG2 overexpression, modulating the expression of TG2 isoforms. It reduced total ROS and O2− production, GFAP and Vimentin levels, inhibiting apoptotic pathway activation. It also induced an increase in the Nestin and cyclin D1 expression levels. Our data demonstrated that indicaxanthin pre-treatment stimulated OECs self-renewal through the reparative activity played by TG2. They also suggest that Aβ might modify TG2 conformation in OECs and that indicaxanthin pre-treatment might modulate TG2 conformation, stimulating neural regeneration in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

3,3-Disubstituted oxindole derivatives bearing a nitrogen atom at the C-3 position have been synthesized starting from 3-alkyl oxindole through a metal free pathway. These derivatives have been tested in five human tumor cell lines (PC3, MCF7, SW620, MiaPaca2 and A375) and on primary cells (PBMCs) from healthy donors providing compound 6d showing a strong anticancer effect in all cancer lines on the low micromolar range. [ABSTRACT FROM AUTHOR]

2-Propargyl-1,3-dicarbonyl compounds have been carbonylated under oxidative conditions and with the catalysis of the PdI 2 /KI catalytic system to selectively afford previously unreported 2-(4-acylfuran-2-yl)acetamides in fair to good yields (54-81%) over 19 examples. The process takes place under relatively mild conditions and occurs via a mechanistic pathway involving C sp -H activation by oxidative monoamincarbonylation of the terminal triple bond of the substrates with formation of 2-ynamide intermediates, followed by 5- exo - dig O -cyclization (via intramolecular conjugate addition of the in situ formed enolate to the 2-ynamide moiety) and aromative isomerization.

A series of azastilbene derivatives, characterized by the presence of the 1,2,4-oxadiazole-5-one system as a linker of the two aromatic rings of stilbenes, have been prepared as novel potential inhibitors of p38 MAPK. Biological assays indicated that some of the synthesized compounds are endowed with good inhibitory activity towards the kinase. Molecular modeling data support the biological results showing that the designed compounds possess a reasonable binding mode in the ATP binding pocket of p38α kinase with a good binding affinity.

Dendrimer-functionalized multi-walled carbon nanotubes (MWCNT) for heavy metal ion removal from wastewaters were developed. Triazole dendrimers (TD) were built directly onto the carbon nanotube surface by successive click chemistry reactions affording the zero- and first-generation dendrimer-functionalized MWCNT (MWCNT-TD1 and MWCNT-TD2). The Moedritzer-Irani reaction carried out on the amino groups present on the MWCNT-TD2 sample gave the corresponding α-aminophosphonate nanosystem MWCNT-TD2P. Both MWCNT-TD2 and MWCNT-TD2P nanosystems have been characterized by physical, chemical, and morphological analyses. Their chelating abilities towards the toxic metal ions Pb 2+ , Hg 2+ , and Ni 2+ and the harmless Ca 2+ ion have been experimentally evaluated in the two different sets of experiments and at the salt concentrations of 1 mg/mL or 1 μg/mL by inductively coupled plasma mass spectrometry (ICP-MS). The results of these studies pointed out the interesting chelating behavior for the phosphonated nanosystem towards the Hg 2+ ion. The complexation mode of the best chelating system MWCNT-TD2P with mercury was investigated through density functional theory (DFT) calculations, suggesting a chelation mechanism involving the two oxygen atoms of the phosphate group. The synthesized dendrimers, supported on the multi-walled carbon nanotubes, have shown the potential to be used for the selective toxic metal ion removal and recovery.

A series of spiro[isoindole-1,5-isoxazolidin]-3(2 H )-ones has been synthesized by 1,3-dipolar cycloaddition of N -benzylnitrone with isoindolin-3-methylene-1-ones. The regio- and stereoselectivity of the process have been rationalized by computational methods. The obtained compounds show cytotoxic properties and antiproliferative activity in the range of 9-22 μM. Biological tests suggest that the antitumor activity could be linked to the inhibition of the protein-protein p53-MDM2 interaction. Docking measurements support the biological data.

AcAlaNH2 ⋅ n H2O (n=1-13) complexes have been proposed as models to account for water solvent effects on the molecular properties of N-acetyl-L-alanine amide. Ab initio computations are planned to evaluate peptide-water interactions and to provide a means for approximating relative effects of the short-range many-body interactions arising in real solution without introducing any external parameters intended to quantify empirical or semiempirical potential-energy functions. The present bottom-up approach reveals the formation of compact ring clusters of water molecules strongly bonded to peptidic polar groups throughout hydrogen bonds. The explicit coordination of water molecules around the peptide renders the fully extended (FE) and polyproline II (PPII) conformers more stable with respect to the 310 helix or γ turn. The alternance of donor and acceptor groups on both sides of the FE and PPII conformers allows for synergy and extensive H-bonding., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Phosphonated nucleosides represent a promising alternative in the improvement of the biological activity of nucleoside analogues in antiviral and anticancer chemotherapy. The basic concept, the chemistry, the different structural modifications and their effects on the antiviral potency will be discussed in this review.