Showing papers by "Maria A. Chiacchio published in 2015"

Synthesis and biological properties of 5-(1H-1,2,3-triazol-4-yl)isoxazolidines: a new class of C-nucleosides.

Abstract: A novel series of C-nucleosides, featuring the presence of a 1,2,3-triazole ring linked to an isoxazolidine system, has been designed as mimetics of the pyrimidine nucleobases. An antiproliferative effect was observed for compounds 17a and 17b: the growth inhibitory effect reaches the 50% in HepG2 and HT-29 cells and increases up to 56% in the SH-SY5Y cell line after 72 h of incubation at a 100 µM concentration.

Copper(II)-Catalyzed Alkoxyhalogenation of Alkynyl Ureas and Amides as a Route to Haloalkylidene-Substituted Heterocycles.

Abstract: A highly effective synthesis of haloalkylidene-substituted heterocycles by copper(II)-catalyzed cyclization of alkynyl ureas and secondary amides has been developed. The reaction, which involves a catalytic amount of CuCl2 and a stoichiometric amount of N-halosuccinimide, occurs selectively through an alkoxyhalogenation process. Alternatively, alkoxychlorination and alkoxybromination reactions can be performed working solely with stoichiometric CuCl2 and CuBr2, respectively.

Interfacial water at the trialanine hydrophilic surface: a DFT electronic structure and bottom-up investigation

Abstract: DFT-M062X quantum chemical computations on the Ala3H+·nH2O (n up to 37) complexes have been performed to model for hydration effects on the molecular properties of protonated trialanine. Following simple rules to arrange water molecules around the peptide, geometry optimization allows us to find four minima corresponding to the unfolded extended (β) and polyproline II (PPII) conformations. The peptide is incorporated into the network of hydrogen bonds of interfacial water molecules with a hydration energy of about −85 kcal mol−1. The progressive hydration of the peptide shows a more efficient intermolecular hydrogen bonding in the PPII arrangement, and the following relative electronic energy stability β–β < β-PPII ≈ PPII-β < PPII–PPII has been found. The conformational entropy term proceeds in the reverse direction, thus these changes compensate in a way that leads to small changes in Gibbs free energy. These findings agree with experimental data which report an equilibrium between these conformers modulated by temperature.

C-5'-Triazolyl-2'-oxa-3'-aza-4'a-carbanucleosides: Synthesis and biological evaluation.

Abstract: A novel series of 2’-oxa-3’-aza-4’a-carbanucleosides, featured with a triazole linker at the 5’-position, has been developed by exploiting a click chemistry reaction of 5’-azido-2’-oxa-3’-aza-4’a-carbanucleosides with substituted alkynes. Biological tests indicate an antitumor activity for the synthesized compounds: most of them inhibit cell proliferation of Vero, BS-C-1, HEp-2, MDCK, and HFF cells with a CC50 in the range of 5.0–40 μM. The synthesized compounds do not show any antiviral activity.

Synthesis and Thermal Behaviour of Novel Aliphatic/Aromatic Hepta-Cyclopentyl Bridged Polyhedral Oligomeric Silsesquioxanes (POSSs)/Polystyrene (PS) Nanocomposites

Abstract: The resistance to the thermal degradation of some polystyrene (PS) based nanocomposites, containing as filler novel aliphatic and aromatic hepta-cyclopentyl bridged polyhedral oligomeric silsesquioxanes (POSSs), was evaluated in both inert and oxidative atmospheres. The fillers were formed by two identical silicon cages R7(SiO1.5)8 (R = cyclopentyl) linked to several aliphatic [–(CH2)2–, –(CH2)6– and –(CH2)10–] and aromatic (Ar, Ar–Ar, Ar–O–Ar and Ar–S–Ar) bridges, where Ar = p-C6H4. Nanocomposites were prepared by in situ polymerization of styrene in the presence of 5 % w/w of appropriate POSS. The actual filler content in the products obtained, checked by 1 H NMR spectroscopy, resulted in all cases slightly higher than in starting mixtures. The glass transition temperature (T g) was also determined by Differential Scanning Calorimetry. The degradation of nanocomposites was carried out into a thermobalance and the temperatures at 5 % mass loss (T 5 %) were determined to evaluate the resistance to the thermal degradation which resulted, for the compounds here studied, higher not only than PS, but also than those of the nanocomposites filled with the corresponding hepta-isobutyl POSSs. The results were compared and discussed and suggested that the increments of resistance to thermal degradation in respect to neat PS (T 5 % of nanocomposite − T 5 % of PS) obey to an additivity group law.

5-(3-Phosphonated 1H-1,2,3-triazol-4-yl)isoxazolidines: synthesis, DFT studies and biological properties

Abstract: Triazolyl-2-methylisoxazolidin-3-yl 3-phosphonates have been synthesized by 1,3-dipolar cycloaddition of N-methyl-C-diethoxyphosphorylnitrone and vinyl triazoles. The process showed a complete regioselectivity and a nearly exclusive cis stereoselectivity. M062X/6-31G(d,p) calculations rationalize the regio- and the stereoc hemical results. The formation of a hydrogen bond along a particular reaction channel significan tly stabilizes both transition states and products related to cis -adducts. Biological tests indicate that the obtain ed compounds do not show relevant antiviral and anticancer activity.

Expression of Tissue Transglutaminase in Human Thyroid Cancer Cell Lines: Effect of Novel Enantiopure Triazole Derivatives

Abstract: A synthesis of (-)5b and (-)6d according to enzymatic resolution of racemic triazole derivatives 5b and 6d was performed with Lipozyme in 1,4-dioxane, using vinyl benzoate as the acyl donor. The effect of the compounds on TG2 overexpression in human thyroid cancer cell lines cultures at two degrees of malignancyand invasiveness was assessed. The involvement of TG2 in the activation of the apoptotic pathway is also shown. We found that the obtained compounds are able to reduce TG2 overexpression in follicular (FTC-133) and anaplastic (8305C) human thyroid cancer cell lines either in the cytosol, or in the nuclear compartment, activating also the apoptotic pathway. Our data suggest that they may represent new anticancer agents for human thyroid cancer.

Copper(II)-Catalyzed Alkoxyhalogenation of Alkynyl Ureas and Amides as a Route to Haloalkylidene-Substituted Heterocycles.

Abstract: A highly effective synthesis of haloalkylidene-substituted heterocycles by copper(II)-catalyzed cyclization of alkynyl ureas and secondary amides has been developed. The reaction, which involves a catalytic amount of CuCl2 and a stoichiometric amount of N-halosuccinimide, occurs selectively through an alkoxyhalogenation process. Alternatively, alkoxychlorination and alkoxybromination reactions can be performed working solely with stoichiometric CuCl2 and CuBr2, respectively.