Ugo Chiacchio

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.

This review is targeted on the synthesis of isoxazolidines as the core of biologically active compounds having anti-cancer, antiviral, antibacterial and anti-inflammatory properties. The isoxazolidine ring, as mimetic of ribose, has been principally synthesized with high regio-, stereo- and enantioselectivity, applying the methodology of 1,3-dipolar cycloaddition, involving nitrones and alkenes as dipoles and dipolarophiles, respectively. The easy accessibility of this ring by this approach, then, makes this heterocycle,particularly suitable for the synthesis of small molecules useful in the design of new and modified drugs.

A palladium-catalyzed diamination domino process of sulfamates arising from glycine allylamides is reported.

The first example of a tandem thionation/S-cyclization process leading to benzo[c]thiophene-1(3H)-thione and 1H-isothiochromene-1-thione derivatives, starting from 2-alkynylbenzoic acids, is reported. The reaction is carried out in CH₂Cl₂ using 1 equiv. of Lawesson's reagent under MW irradiation at 100 °C and 300 W for 1 h. Depending on the nature of the substituent at the distal β carbon of the triple bond, either benzothiophenethiones or isothiochromenethiones were obtained selectively, in high to excellent yields. The structure of the representative compounds has been confirmed by X-ray diffraction analysis.

A novel thermally reversible cross‐linked polymer has been synthesized by a Diels‐Alder (DA) reaction between bis(4‐maleimido‐phenyl)fluorene (cBMI) and tetrakis‐furan monomers (4F) under microwave (MW) irradiation. The ultimate aim of this work was the preparation of a thermosetting material recyclable by a simple thermal treatment. The use of the MW irradiation was necessary because under thermal conditions the DA polymerization could lead to materials only partially cross‐linked for a not desired equilibrium between DA and retro‐DA processes induced by the high temperature. The easy thermal degradation of this cross‐linked material was ascertained by appropriate experiments. Moreover, to better study the involved reactions of formation and decomposition, a more simple model‐compound was also synthesized. The reported data confirm the recyclability of the synthesized cross‐linked polymer by simply heating with the possibility of a regeneration of the polymer network by a further MW irradiation. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 42314.

The review offers an overview on the synthesis of phosphonated N,O-nucleosides, a new class of interesting, potential antiviral/ antitumor agents. The main synthetic method exploit a 1,3- dipolar cycloaddition reaction as key step. The cycloaddition process involves the use of phosphonated nitrones, or nitrones containing functional groups easily convertible into phosphonated group. Biological assays are presented, which show that phosphonated N,O-nucleosides represent a new promising template of nucleoside analogues.

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.

Progression through the S phase of the cell cycle is controlled by cyclin-dependent kinase 2 (CDK2), the activity of which depends on its binding to regulatory partners (cyclins E and A). Deregulation of the activity of CDK2 has been associated with several types of sickness, such as infectious, neurodegenerative, and proliferative diseases. Based on these data, CDK2 has become an attractive target for the development of new anticancer drugs. Indoledione derivatives have recently received special attention in virtue of their pronounced biological effects, such as antiproliferative, antioxidant and antimicrobial properties. In the present work we have investigated the antiproliferative effect of an indolone-based derivative, namely DPIT, whose synthesis we have recently reported, with the aim to clarify its mechanism of action. Furthermore, docking studies have been performed on the eight stereoisomers of DPIT to investigate their capacity to interact as a ligand with ortho- or allosteric sites of CDK2. The encouraging results showed DPIT as a promising candidate for a new type 3 class of inhibitors of CDK2 that recognize the allosteric site.

New calix[4]arene conjugates that present polycyclic aromatic hydrocarbons (PAHs) at their exo rims have been synthesized by esterification of a cone‐shaped calix[4]arenedicarboxylic acid with trans‐ or cis‐pyrenylisoxazolidinyl alcohols prepared by a 1,3‐dipolar cycloaddition methodology. The in vitro cytotoxic activities of all compounds were evaluated with three different human tumor cell lines, and the most potent one reached an IC₅₀ of 95 nM. The different biological activities of the synthesized compounds were explained by docking and circular dichroism studies, which evidenced their intercalating abilities from the DNA minor groove.

The crystal structure of racemic dimethyl (4RS,5RS)-3-(4-nitrophenyl)-4,5-dihydroisoxazole-4,5-dicarboxylate, C₁₃H₁₂N₂O₇, has been determined by single-crystal X-ray diffraction. By analysing the degree of growth of the morphologically important crystal faces, a ranking of the most relevant non-covalent interactions determining the crystal structure can be inferred. The morphological information is considered with an approach opposite to the conventional one: instead of searching inside the structure for the potential key interactions and using them to calculate the crystal habit, the observed crystal morphology is used to define the preferential lines of growth of the crystal, and then this information is interpreted by means of density functional theory (DFT) calculations. Comparison with the X-ray structure confirms the validity of the strategy, thus suggesting this top–down approach to be a useful tool for crystal engineering.