syn / anti Switching by Specific Heteroatom–Titanium Coordination in the Mannich‐Like Synthesis of 2,3‐Diaryl‐β‐amino Acid Derivatives

A very efficient synthesis of 2,3‐diaryl‐β‐amino acid derivatives is realized by a TiCl 4 /triethylamine‐catalyzed Mannich‐like reaction of arylacetic or arylthioacetic esters with arylimines. The presence on the arylacetic moiety of an ortho ‐heteroatom group able to coordinate to the titanium center is of dramatic importance for the outcome of the reaction and to tune the syn / anti diastereoselection. In particular, with o ‐F‐, o ‐Cl‐, and o ‐Br‐arylacetates, the syn adduct was isolated as the largely prevalent isomer. When (–)‐8‐phenylmenthyl (2‐fluorophenyl)acetate was used, the condensation with imines resulted in high diastereo‐ and enantioselectivity. In agreement with the stereochemical results and NMR studies, a conceivable reaction mechanism was proposed.

Brønsted Acid Catalyzed Bisindolization of α‐Amido Acetals: Synthesis and Anticancer Activity of Bis(indolyl)ethanamino Derivatives

A Brønsted acid catalyzed bisindolization reaction with suitable α‐amido acetals that tolerates a wide range of indoles is reported. The method allows rapid access to the biologically relevant bisindolyl ethanamine scaffold in good to excellent yields upon mild amide basic hydrolysis. In preliminary pharmacological studies, some of these compounds display cytotoxic activity in U937 cancer cells. The marine natural alkaloid 2,2‐di(6′‐bromo‐3′‐indolyl)‐ethylamine was the most active compound and could be a lead candidate for further optimization. For the first time, the biological role of this brominated bisindole marine alkaloid is presented.

Synthesis and Biological Activity of Triazole‐Appended N,O‐Nucleosides

1,2,3‐Triazole‐appended N,O‐nucleosides have been synthesized by an approach combining a 1,3‐dipolar cycloaddition process and an alkyne–azide click chemistry reaction. Biological assays, performed on six tumor cell lines, revealed the antiproliferative activity of the synthesized compounds. The effect was more evident in the U87MG human glioblastoma cell line. Thus, these nucleoside analogues could be promising scaffolds for the construction of new anticancer agents.

Chemoselective Synthesis of N ‐Protected Alkoxyprolines under Specific Solvation Conditions

N ‐Protected hydroxyprolines (Hyp) were transformed chemoselectively into alkoxyproline derivatives by direct O ‐alkylation. The starting Hyp was transformed into the corresponding dianion in a mixture of dimethyl sulfoxide and tetrahydrofuran (1:16 v / v ) as solvent. Under these conditions, the carboxy‐anion showed reduced nucleophilicity because it was specifically solvated, and the more reactive oxy‐anion was selectively alkylated. N ‐Protected trans ‐4‐alkoxy‐, cis ‐4‐alkoxy‐ and trans ‐3‐alkoxyprolines were thus obtained in a single step in very high overall yields and with complete stability of the stereogenic center configuration.

Application of direct HPTLC ‐ MALDI for the qualitative and quantitative profiling of neutral and acidic glycosphingolipids: The case of NEU3 overexpressing C2C12 murine myoblasts

Glycosphingolipids (GSLs) are a class of ubiquitous lipids characterized by a wide structural repertoire and a variety of functional implications. Importantly, altered levels have been correlated with different diseases, suggesting their crucial role in health. Conventional methods for the characterization and quantification are based on high‐performance TLC (HPTLC) separation and comparison with the migration distance of standard samples or on MS. We set up and herein report the application of an ImagePrep method for glycosphingolipids qualitative and quantitative profiling through direct HPTLC‐MALDI with particular application to wild‐type and NEU3 sialidase‐overexpressing C2C12 myoblasts. Lipids were analyzed by HPTLC, coupled with MALDI‐TOF, and the resulting GSLs profiles were compared to the [ 3 H]sphingolipids HPTLC patterns obtained after metabolic radiolabeling. GSLs detection by HPTLC‐MALDI was optimized by testing different methods for matrix delivery and by performing quantitative analyses using serial dilutions of GSLs standards. Through this approach an accurate analysis of each variant of neutral and acidic GSLs, including the detection of different fatty‐acid chain variants for each GSL, was provided and these results demonstrated that HPTLC‐MALDI is an easy and high‐throughput analytical method for GSLs profiling, suggesting its use for an early detection of markers in different diseases, including cancer and heart ischemia.

Attempt to run urinary protein electrophoresis using capillary technique

The study of urinary protein has a predominant place in the diagnosis of kidney disease. The most common technique is agarose gel electrophoresis (AGE). For several years, the technique of choice applied to the analysis of serum proteins has been CE, a system that uses capillary fused silica, subjected to high voltage to separate and measure serum proteins. The purpose of this paper was to perform capillary electrophoresis on urinary proteins which, at present, are not interpretable due to the many nonspecific peaks visible when using gel electrophoresis. In order to carry out our research, we used a capillary V8 analyzer together with an agarose gel system from the same company. AGE was taken as the reference method, for which urine was used without any pretreatment. For the V8 system, urine was subjected to purification on granular‐activated carbon and then inserted into the V8 analyzer, selecting a program suitable for liquids with low protein content. We examined 19 urine samples collected over 24 hrs from both hospitalized and external patients with different types of proteinuria plus a serum diluted 1/61 considered as a control to recognize the bands. Both methods showed the same protein fractions and classified the proteinuria in a similar way.

Urea increases fed‐batch growth and γ‐linolenic acid production of nutritionally valuable Arthrospira (Spirulina) platensis cyanobacterium

In this article we investigate the simultaneous influence of feeding time and amount of urea added as a nitrogen source on the fed‐batch growth and composition of Arthrospira ( Spirulina ) platensis . Cultivations were performed in 5‐L minitanks at constant temperature (25°C) and light intensity (42 μmol photons/m 2 s), using exponentially increasing rate of urea addition, and varying the above independent variables in the ranges 9–15 days and 4.6–12.1 mM, respectively. Special emphasis was placed on the content of added high value fatty acids (e.g., γ‐linolenic acid) of concern for the food industry. To this purpose, a 2 2 ‐plus star central composite design was employed, and maximum cell concentration, cell productivity, yield of biomass on nitrogen added, protein content and fatty acids profile were evaluated by multiple regression analysis. The highest cell concentration (1759 mg/L) was obtained at feeding time of 14 days and amount of urea per unit reactor volume of 5.8 mM, while the highest contents of γ‐linolenic acid (27.5% of the lipid fraction) and proteins (77.2%) were obtained at 10 and 14 days and 5.8 and 10.8 mM, respectively. The results confirm the possibility of using urea as cheap nitrogen source to culture this nutritionally valuable cyanobacterium.

The Fragile X Protein binds mRNA s involved in cancer progression and modulates metastasis formation

Central and Peripheral Peptides Regulating Eating Behaviour and Energy Homeostasis in Anorexia Nervosa and Bulimia Nervosa: A Literature Review

A large body of literature suggests the occurrence of a dysregulation in both central and peripheral modulators of appetite in patients with anorexia nervosa (AN) and bulimia nervosa (BN), but at the moment, the state or trait‐dependent nature of those changes is far from being clear. It has been proposed, although not definitively proved, that peptide alterations, even when secondary to malnutrition and/or to aberrant eating behaviours, might contribute to the genesis and the maintenance of some symptomatic aspects of AN and BN, thus affecting the course and the prognosis of these disorders. This review focuses on the most significant literature studies that explored the physiology of those central and peripheral peptides, which have prominent effects on eating behaviour, body weight and energy homeostasis in patients with AN and BN. The relevance of peptide dysfunctions for the pathophysiology of eating disorders is critically discussed. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Age‐related biological features of germ cell tumors

Germ cell tumors (GCTs) are rare but clinically and pathologically diverse tumors that occur in an extensive range of age groups, from children to older adults and which include both seminomatous and nonseminomatous tumors. Current clinical management for both male and female teenagers and young adults (TYAs) with GCTs remains inconsistent, alternating between pediatric and adult multidisciplinary oncology teams, based on locally defined age cutoffs. Therefore, we reviewed available literature to determine the biological similarities and differences between GCTs in young children (0–12 years), TYAs (13–24 years), and older adults (>24 years). GCTs arising in pediatric and adult populations in general showed marked molecular biological differences within identical histological subtypes, whereas there was a distinct paucity of available data for GCTs in the TYA population. These findings highlight that clinical management based simply on chronological age may be inappropriate for TYA and suggests that the optimal future management of GCTs should consider specific molecular biological factors in addition to clinical parameters in the context of patient‐specific age group rather than medical specialty. © 2013 Wiley Periodicals, Inc.