Symmetrical α-bromoacryloylamido diaryldienone derivatives as a novel series of antiproliferative agents. Design,synthesis and biological evaluation

In a continuing study of hybrid compounds containing the α-bromoacryloyl moiety as potential anticancer drugs, we synthesized a novel series of hybrids 4a–h, in which this moiety was linked to a 1,5-diaryl-1,4-pentadien-3-one system. Many of the conjugates prepared (4b, 4c, 4e and 4g) demonstrated pronounced, submicromolar antiproliferative activity against four cancer cell lines. Moreover, compound 4b induced apoptosis through the mitochondrial pathway and activated caspase-3 in a concentration-dependent manner.     

Taxonomic features ofSesleria calabrica (Poaceae), a neglected species from southern Italy

A taxonomic study of theSesleria juncifolia complex in the Italian Peninsula is presented, with a focus on southern Italian populations here named asSesleria calabrica (Deyl)Di Pietro comb. nov. et stat. nov. Karylological, morphological and anatomical characters were used for comparative analyses with populations of closely related species, such asS. juncifolia Suffren andSesleria apennina Ujhelyi occurring in the Italian Peninsula. Multivariate and univariate morphometric analyses, and qualitative morphological characters showed a distinct position ofS. calabrica. Populations ofS. calabrica differ in respect to various morphological characters of leaf and spikelet, such as the glume, lemma and palea length, stem length, the leaf sheath, leaf width, leaf thickness, and the total number of vascular bundles. Furthermore, previous karyological studies demonstrated that all the populations of bothS. juncifolia andS. apennina examined are octopolid (2n=8x=56), whereasS. calabrica was found to be dodecaploid (2n=12x=84).S. calabrica is strictly confined to the Pollino massif and the Orsomarso mountains in southern Italy, which represent the southernmost limit of theSesleria juncifolia complex distribution area both in Italy and in Europe. In addition toS. juncifolia andS. calabrica, the recognition ofS. apennina as a taxon distinct fromS. juncifolia is supported, at least for the area of the Apuan Alps.     

Effects of moderate beer consumption on first-line immunity of healthy adults

Moderate alcohol consumption has shown to induce benefits on host specific (cell-mediated and humoral) immune system, but there is scarce literature regarding first-line immune responses. The aim of this study was to investigate differences in non-specific immunity after alcohol abstention and moderate beer consumption in healthy adults. After a 30 day-alcohol abstemious period, 57 healthy volunteers were submitted to a daily moderate consumption of beer (330 mL for women and 660 mL for men, respectively) during the following 30 days. White blood cell counts and phagocytic and oxidative burst activity were evaluated at three points: a) basal, b) abstemious, c) after moderate consumption of beer. Absolute values of leukocytes, neutrophils, lymphocytes and basophiles (x10(9)/L) increased significantly in women from point b to point c (6.34 +/- 1.26 vs. 7.27 +/- 1.97, 3.43 +/- 0.88 vs. 4.13 +/- 1.53, 2.14 +/- 0.50 vs. 2.38 +/- 0.63, and 0.05 +/- 0.02 vs. 0.06 +/- 0.03, respectively; p < 0.05) as well as basophils in men (0.05 +/- 0.03 vs. 0.06 +/- 0.03). A significant increase of oxidative burst capacity was also observed after the moderate consumption of beer in both women (33.90 +/- 19.00 vs. 48.86 +/- 21.83) and men (27.39 +/- 18.13 vs. 39.25 +/- 24.53). In healthy adults, after 30 days of moderate beer consumption the parameter describing the non-specific immunity improved when compared to the basal situation. For several of these parameters, the response is more enhanced in women.     

Encapsulation and exfoliation of inorganic lamellar fillers into polycaprolactone by electrospinning

The present paper reports, for the first time, the successful fabrication of layered double hydroxide (Mg-Al LDH)-reinforced polycaprolactone (PCL) nanofibers by electrospinning. Either the LDH in carbonate form or an LDH organically modified with 12-hydroxydodecanoic acid (LDH-HA) were incorporated into PCL and electrospun using a voltage of 20 KV. The LDH-HA was prepared by an ionic exchange reaction from pristine LDH and encapsulated into PCL from acetone solutions at 15 wt %. The morphological analysis showed pure PCL fibers with an average diameter of 600 +/- 50 nm, and this dimension was maintained in the fibers with LDH, with the inorganic component residing outside the fibers and not exfoliated. At variance, the fibers with the LDH-HA showed a significantly lower average diameter in the range of 350 +/- 50 nm, indicating the improved electrospinnability of PCL. Moreover, the inorganic lamellae were exfoliated, as shown by X-rays and residing inside the nanofibers as demonstrated by energy dispersive X-ray spectroscopy analysis. The structural parameters, such as degradation temperature and crystallinity, were investigated for all the samples and correlated with the electrospinning process.     

Synthesis of novel antimitotic agents based on 2-amino-3-aroyl-5-(hetero)arylethynyl thiophene derivatives

Microtubules are dynamic structures that play a crucial role in cellular division and are recognized as an important target for cancer therapy. In search of new compounds with strong antiproliferative activity and simple molecular structure, a new series of 2-amino-3-(3′,4′,5′-trimethoxybenzoyl)-5-(hetero)aryl ethynyl thiophene derivatives was prepared by the Sonogashira coupling reaction of the corresponding 5-bromothiophenes with several (hetero)aryl acetylenes. When these compounds were analyzed in vitro for their inhibition of cell proliferation, the 2- and 3-thiophenyl acetylene derivatives were the most powerful compounds, both of which exerted cytostatic effects at submicromolar concentrations. In contrast, the presence of a more flexible ethyl chain between the (hetero)aryl and the 5-position of the thiophene ring resulted in significant reduction in activity relative to the 5-(hetero)aryl acetylene substituted derivatives. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. We found that the antiproliferative effects of the most active compounds were associated with increase of the proportion of cells in the G₂/M and sub-G₁ phases of the cell cycle.     

Antiviral activity of seed extract from Citrus bergamia towards human retroviruses

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.     

The agent is right: when motor embodied cognition is space-dependent

The role of embodied mechanisms in processing sentences endowed with a first person perspective is now widely accepted. However, whether embodied sentence processing within a third person perspective would also have motor behavioral significance remains unknown. Here, we developed a novel version of the Action-sentence Compatibility Effect (ACE) in which participants were asked to perform a movement compatible or not with the direction embedded in a sentence having a first person (Experiment 1: You gave a pizza to Louis) or third person perspective (Experiment 2: Lea gave a pizza to Louis). Results indicate that shifting perspective from first to third person was sufficient to prevent motor embodied mechanisms, abolishing the ACE. Critically, ACE was restored in Experiment 3 by adding a virtual "body" that allowed participants to know "where" to put themselves in space when taking the third person perspective, thus demonstrating that motor embodied processes are space-dependent. A fourth, control experiment, by dissociating motor response from the transfer verb's direction, supported the conclusion that perspective-taking may induce significant ACE only when coupled with the adequate sentence-response mapping.