Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities

The natural product lupeol 1 was isolated from aerial parts of Vernonia scorpioides with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives 2–11 were prepared by classical procedures. Including, five new esters derivatives 7–11, which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol 1–11 were confirmed by ¹H NMR, ¹³C NMR and HRMS. Their antiprotozoal activity was evaluated in vitro against L. amazonensis and T. cruzi. Derivative 6 showed the best antitrypanosomal activity (IC₅₀ = 12.48 μg/mL) and the lowest cytotoxic derivative (CC₅₀ = 161.50 μg/mL). The mechanism of action of the most active derivatives (4, 6 and 11) is not dependent from the enzyme trypanothione reductase.     

Dynamic response of rocking cracked masonry walls

The behaviour of masonry constructions results to be very far from the one characterizing ductile structures. In masonry constructions, the seismic action activates a rocking motion rather than a dissipating mechanism. A strength resource of masonry structures, properly reinforced in order to avoid early local failures, consists in exhibiting rocking behaviour, until a failure condition is attained. Aim of the paper is to investigate the dynamic behaviour of masonry single storey walls, according to Housner’s studies and innovatively introducing the effect of diagonal cracks developing from the toes of the piers and shown by typical post-earthquake cracking patterns. The proposed procedure can be easily applied to the case of multi-storey regular masonry walls with openings representing the main resistant structural components of a masonry building. Starting from the evaluation of the incipient rocking acceleration of the system, the free and forced motions of the wall are examined. In the paper, according to the classical Housner’s approach, the energy dissipation occurring during the impact is modelled. Finally, a numerical application, considering a simple constant horizontal acceleration impulse of given duration has been carried out.

     

Facile Tailoring of Structures for Controlled Release of Paracetamol from Sustainable Lignin Derived Platforms

Nowadays, sustainable materials are receiving significant attention due to the fact that they will be crucial for the development of the next generation of products and devices. In the present work, hydrogels have been successfully synthesized using lignin which is non-valorized biopolymer from the paper industry. Hydrogels were prepared via crosslinking with Poly(ethylene) glycol diglycidyl ether (PEGDGE). Different crosslinker ratios were used to determine their influence on the structural and chemical properties of the resulting hydrogels. It has been found that pore size was reduced by increasing crosslinker amount. The greater crosslinking density increased the swelling capacity of the hydrogels due to the presence of more hydrophilic groups in the hydrogel network. Paracetamol release test showed higher drug diffusion for hydrogels produced with a ratio lignin:PEGDGE 1:1. The obtained results demonstrate that the proposed approach is a promising route to utilize lignocellulose waste for producing porous materials for advanced biomedical applications in the pharmacy industry.     

Studies on the collision‐induced dissociation of adipoR agonists after electrospray ionization and their implementation in sports drug testing

AdipoR agonists are small, orally active molecules capable of mimicking the protein adiponectin, which represents an adipokine with antidiabetic and antiatherogenic effects. Two adiponectin receptors were reported in the literature referred to as adipoR1 and adipoR2. Activation of these receptors stimulates mitochondrial biogenesis and results in an improved oxidative metabolism (via adipoR1) and increased insulin sensitivity (via adipoR2). Hence, adipoR agonists are potentially performance enhancing substances and targets of proactive and preventive anti‐doping measures. In this study, two adipoR agonists termed AdipoRon and 112254 as well as two isotopically labeled internal standards (ISTDs) were synthesized in three‐step reactions. The products were fully characterized by nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS) and density functional theory (DFT) computation. Collision‐induced dissociation pathways following electrospray ionization were suggested based on the determined elemental compositions of product ions, comparison to product ions derived from labeled analogs (ISTDs), H/D‐exchange experiments and the results of DFT calculations. The most abundant product ions were found at m/z 174, tentatively assigned to protonated 1‐benzyl‐1,2,3,4‐tetrahydropyridine for AdipoRon, and m/z 207, suggested as protonated 1‐(4‐methoxybenzyl)piperazine, for 112254. Notably, the loss of the heterocyclic ring (i.e. piperazine and piperidine, respectively) in a supposedly intramolecular elimination reaction was observed in both cases. A qualitative determination of both AdipoR agonists in human plasma was established and fully validated for doping control purposes. Validation items such as recovery (86–89%), specificity, linearity, lower limit of detection (1 ng/ml), intraday (3–18%) and interday (5–16%) precision as well as ion suppression or enhancement were determined. Based on these findings adipoR agonists can be implemented in sports drug testing procedures. Copyright © 2015 John Wiley & Sons, Ltd.