Synthesis and Anti-Trypanosoma cruzi Biological Evaluation of Novel 2-Nitropyrrole Derivatives

Human American trypanosomiasis, called Chagas disease, caused by T. cruzi protozoan infection, represents a major public health problem, with about 7000 annual deaths in Latin America. As part of the search for new and safe anti-Trypanosoma cruzi derivatives involving nitroheterocycles, we report herein the synthesis of ten 1-substituted 2-nitropyrrole compounds and their biological evaluation. After an optimization phase, a convergent synthesis methodology was used to obtain these new final compounds in two steps from the 2-nitropyrrole starting product. All the designed derivatives follow Lipinski’s rule of five. The cytotoxicity evaluation on CHO cells showed no significant cytotoxicity, except for compound 3 (CC₅₀ = 24.3 µM). Compound 18 appeared to show activity against T. cruzi intracellular amastigotes form (EC₅₀ = 3.6 ± 1.8 µM) and good selectivity over the vero host cells. Unfortunately, this compound 18 showed an insufficient maximum effect compared to the reference drug (nifurtimox). Whether longer duration treatments may eliminate all parasites remains to be explored.     

Sequence of polymers by mass spectrometry

Mass Spectrometry, being able to look at the mass of individual molecules in a mixture of homologues, is particularly suitable for the detection of a series of oligomers. However, mass spectra had not been exploited to estimate oligomers distributions, due to the diffuse notion that a lack of correlation existed between peak intensities and concentration of the oligomers in the mixture. The introduction of soft-ionization techniques has largely eliminated this problem. A novel method for the determination of the microstructure of copolymers is presented here. We have recently found that opportune decoding of the information contained in the mass spectral intensities leads to the determination of composition and microstructure in copolymers, and this represents a significant progress. Statistical modeling of the mass spectral intensities of copolymers has been used to derive information on the distribution of monomers along the copolymer chain, and an automated procedure to find the composition and the sequence of the copolymers analyzed has been developed. The statistical analysis of copolymers makes use of Bernoullian and Markovian models in order to characterize the microstructure of copolymer samples, and assuming a theoretical distribution and then fitting the calculated oligomer abundances with the experimental MS peak intensities, the copolymer composition can be determined. A method is also reported to obtain the copolymer conposition by direct analysis of the mass spectra. These theories have been applied to determine the composition and the microstructure of several copolymers whose mass spectra have been reported in the most recent literature.     

Analysis of Pseudo-Lyapunov Exponents of Solar Convection Using State-of-the-Art Observations

The solar photosphere and the outer layer of the Sun’s interior are characterized by convective motions, which display a chaotic and turbulent character. In this work, we evaluated the pseudo-Lyapunov exponents of the overshooting convective motions observed on the Sun’s surface by using a method employed in the literature to estimate those exponents, as well as another technique deduced from their definition. We analyzed observations taken with state-of-the-art instruments at ground- and space-based telescopes, and we particularly benefited from the spectro-polarimetric data acquired with the Interferometric Bidimensional Spectrometer, the Crisp Imaging SpectroPolarimeter, and the Helioseismic and Magnetic Imager. Following previous studies in the literature, we computed maps of four quantities which were representative of the physical properties of solar plasma in each observation, and estimated the pseudo-Lyapunov exponents from the residuals between the values of the quantities computed at any point in the map and the mean of values over the whole map. In contrast to previous results reported in the literature, we found that the computed exponents hold negative values, which are typical of a dissipative regime, for all the quantities derived from our observations. The values of the estimated exponents increase with the spatial resolution of the data and are almost unaffected by small concentrations of magnetic field. Finally, we showed that similar results were also achieved by estimating the exponents from residuals between the values at each point in maps derived from observations taken at different times. The latter estimation technique better accounts for the definition of these exponents than the method employed in previous studies.     

Quality of Service Measurements over an Optical GMPLS Wide Area Access Network

The introduction of intelligence for management and control of optical networks based on internet protocol and the quality of service (QoS) are key issues for the evolution of the next generation network. In this paper the authors report experimental results on QoS measurements related to different real time multimedia services in an optical network based on a ring configuration obtained by means of the fibers contained in an installed cable between Rome and Pomezia, core routers with optical Gigabit Ethernet interfaces and configured with differentiated service over multi-protocol label switching architecture.     

Combinatorial peptide ligand libraries: the conquest of the 'hidden proteome' advances at great strides

The combinatorial peptide ligand library (CPLL) is compared here with the immuno-depletion method for evaluating their respective abilities in digging deeper and deeper into the low-abundance proteome. A recent report suggested in fact that immuno-subtraction for biomarkers discovery in sera does not perform so well, since it results in a meagre 25% increase in identified proteins compared with unfractionated plasma, leaving little capacity to sample lower abundance proteins. On the contrary, CPLLs permit from 300 to 600% increments in detection abilities, as amply demonstrated in several reports. Moreover, when dealing with large sample volumes, an amplification factor of up to four orders of magnitude for trace proteins could be demonstrated, with 80% capture efficiencies even in large (up to 1?L) sample volumes. At present, the lower detection ability of CPLLs has been evaluated at 1?ng/mL (traces of casein additives in white wines).     

Inversion of configuration of alcohols through nucleophilic displacement promoted by nitrate ions.

Inversion of configuration of hydroxy functionalities in biologically significant structures has been performed under mild conditions through nucleophilic displacement by nitrate ion.     

Research on nitrogen containing heterocyclic compounds. XVI. Synthesis of 1, 3, 4, 14b-tetrahydro-2, 10-dimethyl-2H,10H-pyrazino[2, 1-d]pyrrolo[1, 2-b][1, 2, 5]benzotriazepine (1:1) maleate (10-methyl-10-azaaptazepine)

A synthesis of the potential antidepressant 1, 3, 4, 14b-tetrahydro-2, 10-ditnethyl-2H,10H-pyrazino[2, 1-d]-pyrrolo[1, 2-b][1, 2, 5]benzotriazepine 4 , structurally related to aptazepine, is reported in four steps. The key steps of the synthesis were the formation of the tricyclic compound ethyl 10, 11-dihydro-5-methyl-5H-pyrrolo[1, 2-6-b][1, 2, 5]benzotriazepine-11-carboxylate 6 via a Pictet-Spengler type condensation and the formation of the diketopiperazine 8 by cyclization of the chloroester 7 with methylamine.     

N-methyl-D-glucamine improves the laser-induced fluorescence capillary electrophoresis performance in the total plasma thiols measurement

We describe an ultrarapid capillary electrophoresis with laser-induced fluorescence (CE-LIF) method for total plasma thiols measurement. Reduced thiols by 10% tri-n-butylphosphine (TBP) were derivatized in 10 min at room temperature with 5-iodoacetamidofluorescein (5-IAF) as fluorescent reagent. We show that CE-LIF allows a baseline separation of total plasma cysteinylglycine, homocysteine, cysteine, and glutathione in less than 5 min when N-methyl-D-glucamine in run buffer was added. CE was compared with high-performance liquid chromatography (HPLC) with fluorescence detection. The Bland-Altman test and Passing-Bablok regression demonstrates that the results obtained by CE-LIF and by HPLC are highly comparable. The simplified procedure of sample preparation, the short incubation and fast separation times, the high specificity, sensitivity and reproducibility, and the lower cost of analysis suggest that our proposed method can be considered valuable for the automation analysis in a routine laboratory.     

Development of a Tumor‐Specific Photoactivatable Doxorubicin Prodrug

This is a retrospective highlight on the publication by Ibsen and coworkers: Localized In Vivo Activation of a Photoactivatable Doxorubicin Prodrug in Deep Tumor Tissue, which appeared in a preceding issue of Photochem. Photobiol. (2013, 89:698–708). The authors describe the synthesis and properties of a novel doxorubicin (DOX) prodrug, DOX‐PCB, which contains a photocleavable linker group. Systemic administration of the prodrug to a tumor‐bearing animal followed by LED/fiber optic 365 nm light delivery allowed active DOX to be released site specifically in the tumor area. This elegant and timely study provides compelling evidence that photocleavable DOX‐PCB can eliminate many of the toxic side effects of DOX that have plagued clinical use of this highly effective antitumor drug for many years.