Semisynthesis of Selenoauraptene

Selenium-containing compounds are gaining more and more interest due to their valuable and promising pharmacological properties, mainly as anticancer and antioxidant agents. Ebselen, the up to now only approved drugs, is well known to possess very good glutathione peroxidase mimicking effects. To date, the most of efforts have been directed to build pure synthetic Se containing molecules, while less attention have been devoted to Se-based semisynthetic products resembling natural compounds like terpenes, polyphenols, and alkaloids. The aim of this short communication is to report the synthesis of the first example of a Se-phenylpropanoids, namely selenoauraptene, containing a selenogeranyl side chain in position 7 of the umbelliferone core. The key step was the Newman-Kwart rearrangement to obtain a selenocarbamate in which the Se atom was directly attached to umbelliferone (replacing its 7-OH function) followed by hydrolysis to get diumbelliferyl diselenide, which was finally easily converted to the desired Se-geranyl derivative in quite a good overall yield (28.5%). The synthesized adduct displayed a greater antioxidant and a radical scavenger in vitro activity than parent auraptene. The procedure we describe herein, to the best of our knowledge for the first time in the literature, represents an easy-to-handle method for the synthesis of a wide array of seleno analogues of naturally occurring biologically active oxyprenylated secondary metabolites.     

Macrophage Migration Inhibitory Factor (MIF) and Its Homologue D-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus

Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.     

A numerical methodology for thermo-fluid dynamic modelling of tyre inner chamber: towards real time applications

Meccanica - The characterization and reproduction of tyre behaviour for vehicle modelling is a topic of particular interest both for real-time driver in the loop simulations and for offline...     

7-Isopentenyloxycoumarin: What Is New across the Last Decade

7-Isopentenyloxycoumarin is among the most widespread naturally occurring prenyloxy umbelliferone derivatives. This secondary metabolite of mixed biosynthetic origin has been typically isolated from plants belonging to several genera of the Rutaceae and Apiaceae families, comprising widely used medicinal plants and in general plants with beneficial effects on human welfare, as well as edible fruits and vegetables. Although known for quite a long time (more than 50 years), only in the last two decades has this natural compound been revealed to exert powerful and promising pharmacological properties, such as active cancer chemopreventive, antibacterial, antiprotozoal, antifungal, anti-inflammatory, neuroprotective, and antioxidant properties, among the activities best outlined in the recent literature. The aim of this comprehensive miniature review article is to detail the novel natural sources and the effects described during the last decade for 7-isopentenyloxycoumarin and what has been reported on the mechanisms of action underlying the observed biological activities of this oxyprenylated secondary metabolite. In view of the herein described data, suggestions on how to address future research on the abovementioned natural product and structurally related derivatives in the best ways according to the authors will be also provided.     

Analysis of world terror networks from the reduced Google matrix of Wikipedia

We apply the reduced Google matrix method to analyze interactions between 95 terrorist groups and determine their relationships and influence on 64 world countries. This is done on the basis of the Google matrix of the English Wikipedia (2017) composed of 5 416 537 articles which accumulate a great part of global human knowledge. The reduced Google matrix takes into account the direct and hidden links between a selection of 159 nodes (articles) appearing due to all paths of a random surfer moving over the whole network. As a result we obtain the network structure of terrorist groups and their relations with selected countries including hidden indirect links. Using the sensitivity of PageRank to a weight variation of specific links we determine the geopolitical sensitivity and influence of specific terrorist groups on world countries. The world maps of the sensitivity of various countries to influence of specific terrorist groups are obtained. We argue that this approach can find useful application for more extensive and detailed data bases analysis.     

Absolute configuration of diterpenoids from Jatropha dioica by vibrational circular dichroism

The absolute configuration of jatropholone A 1 and B 2, including the possibility to observe the vibrational circular dichroism (VCD) capacity to differentiate between two epimeric compounds in the presence of an inherently dissymmetric chromophore, which normally dominates VCD and electronic circular dichroism (ECD) spectra, followed after comparison of their experimental and DFT calculated VCD spectra, allowed us to conclude that although non-local (M/P) chirality generated by atropisomerism dominates over local chirality generated by an (R/S) change, the stereogenic center can confidently be assigned by VCD after DFT calculations. In addition, the absolute configurations of jatrophatrione 3 and citlalitrione 4, a compound proposed as a taxonomic marker for the genus Jatropha, were assigned by contrasting their respective calculated and experimental IR and VCD spectra. The evaluation of Flack and Hooft parameters obtained from the single-crystal X-ray diffraction data of jatropholone B acetate 6, and of 4 independently confirmed the absolute configurations of these molecules.