Development of Phenothiazine Hybrids with Potential Medicinal Interest: A Review

The molecular hybridization approach has been used to develop compounds with improved efficacy by combining two or more pharmacophores of bioactive scaffolds. In this context, hybridization of various relevant pharmacophores with phenothiazine derivatives has resulted in pertinent compounds with diverse biological activities, interacting with specific or multiple targets. In fact, the development of new drugs or drug candidates based on phenothiazine system has been a promising approach due to the diverse activities associated with this tricyclic system, traditionally present in compounds with antipsychotic, antihistaminic and antimuscarinic effects. Actually, the pharmacological actions of phenothiazine hybrids include promising antibacterial, antifungal, anticancer, anti-inflammatory, antimalarial, analgesic and multi-drug resistance reversal properties. The present review summarizes the progress in the development of phenothiazine hybrids and their biological activity.     

A comparative study of calibration transfer methods for determination of gasoline quality parameters in three different near infrared spectrometers

This work presents a comparative study of calibration transfer among three near infrared spectrometers for determination of naphthenes and RON (Research Octane Number) in gasoline. Seven transfer methods are compared: direct standardization (DS), piecewise direct standardization (PDS), orthogonal signal correction (OSC), reverse standardization (RS), piecewise reverse standardization (PRS), slope and bias correction (SBC) and model updating (MU). Two pre-treatment procedures, namely standard normal variate (SNV) and multiplicative scatter correction (MSC), are also investigated. The choice of an appropriate number of transfer samples for each technique, as well as the effect of window size in PDS/PRS and OSC components, are discussed. A broad set of gasoline samples representative of the Northeastern states of Brazil is employed in the investigation. The results show that the use of calibration transfer yields prediction errors comparable to those obtained with complete recalibration of the secondary instrument. Overall, the results point to RS as the best method for the analytical problem under consideration. When storage and/or physical transportation of transfer samples are impractical, MU is more appropriate. The comprehensive investigation carried out in the present work will be of value for practitioners involved in networks of fuel monitoring.     

Electrospray ionization mass spectrometry and partial least squares discriminant analysis applied to the quality control of olive oil

Direct infusion electrospray ionization mass spectrometry in the positive ion mode [ESI(+)‐MS] is used to obtain fingerprints of aqueous–methanolic extracts of two types of olive oils, extra virgin (EV) and ordinary (OR), as well as of samples of EV olive oil adulterated by the addition of OR olive oil and other edible oils: corn (CO), sunflower (SF), soybean (SO) and canola (CA). The MS data is treated by the partial least squares discriminant analysis (PLS‐DA) protocol aiming at discriminating the above‐mentioned classes formed by the genuine olive oils, EV (1) and OR (2), as well as the EV adulterated samples, i.e. EV/SO (3), EV/CO (4), EV/SF (5), EV/CA (6) and EV/OR (7). The PLS‐DA model employed is built with 190 and 70 samples for the training and test sets, respectively. For all classes (1–7), EV and OR olive oils as well as the adulterated samples (in a proportion varying from 0.5 to 20.0% w/w) are properly classified. The developed methodology required no ions identification and demonstrated to be fast, as each measurement lasted about 3 min including the extraction step and MS analysis, and reliable, because high sensitivities (rate of true positives) and specificities (rate of true negatives) were achieved. Finally, it can be envisaged that this approach has potential to be applied in quality control of EV olive oils. Copyright © 2013 John Wiley & Sons, Ltd.     

Li8Si8, Li10Si9, and Li12Si10: Assemblies of Lithium-Silicon Aromatic Units

We report the global minima structures of Li₈Si₈, Li₁₀Si₉, and Li₁₂Si₁₀ systems, in which silicon moieties maintain structural and chemical bonding characteristics similar to those of their building blocks: the aromatic clusters T_d−Li₄Si₄ and C_2v−Li₆Si₅. Electron counting rules, chemical bonding analysis, and magnetic response properties verify the silicon unit‘s aromaticity persistence. This study demonstrates the feasibility of assembling silicon-based nanostructures from aromatics clusters as building blocks.     

Immunomodulatory Properties of Masticadienonic Acid and 3α-Hydroxy Masticadienoic Acid in Dendritic Cells

Dendritic cells are antigen-presenting cells, which identify and process pathogens to subsequently activate specific T lymphocytes. To regulate the immune responses, DCs have to mature by the recognition of TLR ligands, TNFα or IFNγ. These ligands have been used as adjuvants to activate DCs in situ or in vitro, with toxic effects. It has been shown that some molecules affect the immune system, e.g., Masticadienonic acid (MDA) and 3α-hydroxy masticadienoic acid (3α-OH MDA) triterpenes naturally occurring in several medicinal plants, since they activate the nitric oxide synthase in macrophages and induce T lymphocyte proliferation. The DCs maturation induced by MDA or 3a-OH MDA was determined by incubating these cells with MDA or 3α-OH MDA, and their phenotype was afterwards analyzed. The results showed that only 3α-OH MDA was able to induce DCs maturation. When mice with melanoma were inoculated with DCs/3α-OH MDA, a decreased tumor growth rate was observed along with an extended cell death area within tumors compared to mice treated with DCs incubated with MDA. In conclusion, it is proposed that 3α-OH MDA may be an immunostimulant molecule. Conversely, it is proposed that MDA may be a molecule with anti-inflammatory properties.     

A Note on Feynman Path Integral for Electromagnetic External Fields

We propose a Fresnel stochastic white noise framework to analyze the nature of the Feynman paths entering on the Feynman Path Integral expression for the Feynman Propagator of a particle quantum mechanically moving under an external electromagnetic time-independent potential.     

CaII Binding Regulates and Dominates the Reactivity of a Transition‐Metal‐Ion‐Dependent Diesterase from Mycobacterium tuberculosis

The diesterase Rv0805 from Mycobacterium tuberculosis is a dinuclear metallohydrolase that plays an important role in signal transduction by controlling the intracellular levels of cyclic nucleotides. As Rv0805 is essential for mycobacterial growth it is a promising new target for the development of chemotherapeutics to treat tuberculosis. The in vivo metal‐ion composition of Rv0805 is subject to debate. Here, we demonstrate that the active site accommodates two divalent transition metal ions with binding affinities ranging from approximately 50 nm for Mn^II to about 600 nm for Zn^II. In contrast, the enzyme GpdQ from Enterobacter aerogenes, despite having a coordination sphere identical to that of Rv0805, binds only one metal ion in the absence of substrate, thus demonstrating the significance of the outer sphere to modulate metal‐ion binding and enzymatic reactivity. Ca^II also binds tightly to Rv0805 (K_d≈40 nm ), but kinetic, calorimetric, and spectroscopic data indicate that two Ca^II ions bind at a site different from the dinuclear transition‐metal‐ion binding site. Ca^II acts as an activator of the enzymatic activity but is able to promote the hydrolysis of substrates even in the absence of transition‐metal ions, thus providing an effective strategy for the regulation of the enzymatic activity.     

Unified QSAR & network‐based computational chemistry approach to antimicrobials. II. Multiple distance and triadic census analysis of antiparasitic drugs complex networks

In the previous work, we reported a multitarget Quantitative Structure‐Activity Relationship (mt‐QSAR) model to predict drug activity against different fungal species. This mt‐QSAR allowed us to construct a drug–drug multispecies Complex Network (msCN) to investigate drug–drug similarity (González‐Díaz and Prado‐Prado, J Comput Chem 2008, 29, 656). However, important methodological points remained unclear, such as follows: (1) the accuracy of the methods when applied to other problems; (2) the effect of the distance type used to construct the msCN; (3) how to perform the inverse procedure to study species–species similarity with multidrug resistance CNs (mdrCN); and (4) the implications and necessary steps to perform a substructural Triadic Census Analysis (TCA) of the msCN. To continue the present series with other important problem, we developed here a mt‐QSAR model for more than 700 drugs tested in the literature against different parasites (predicting antiparasitic drugs). The data were processed by Linear Discriminate Analysis (LDA) and the model classifies correctly 93.62% (1160 out of 1239 cases) in training. The model validation was carried out by means of external predicting series; the model classified 573 out of 607, that is, 94.4% of cases. Next, we carried out the first comparative study of the topology of six different drug–drug msCNs based on six different distances such as Euclidean, Chebychev, Manhattan, etc. Furthermore, we compared the selected drug–drug msCN and species–species mdsCN with random networks. We also introduced here the inverse methodology to construct species–species msCN based on a mt‐QSAR model. Last, we reported the first substructural analysis of drug–drug msCN using Triadic Census Analysis (TCA) algorithm. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010     

Li‐doped nanosized TiO2 powder with enhanced photocalatylic acivity under sunlight irradiation

This work reports on the synthesis of Li‐doped TiO₂ nanoparticles using the sol–gel process and solid‐state sintering, and investigates their potential use as a photocatalyst for degradation under sunlight excitation of different organic model compounds in aqueous solution. The structure of the nanocrystals was examined by X‐ray diffraction, UV‐vis ground state diffuse reflectance absorption spectra and X‐ray photoelectron emission spectroscopy. Results showed that samples prepared by sol–gel process and calcined at 400 °C are composed of a mixture of anatase and rutile phases, in contrast to the one prepared by solid‐state sintering, which exhibits an anatase phase with Li being involved in a spinel phase. The photocatalytic degradation of aqueous solutions of different aromatic compounds was successfully achieved under sunlight excitation in presence of Li‐doped TiO₂ prepared via sol–gel process. It was shown that the calcination temperature and the preparation mode greatly affect the photocatalytic efficiency. Copyright © 2010 John Wiley & Sons, Ltd.     

From superhydrophobic‐ to superhydrophilic‐patterned poly(vinylidene fluoride‐co‐chlorotrifluoroethylene) architectures as a novel platform for biotechnological applications

The manufacture of three‐dimensional patterned electroactive poly(vinylidene fluoride‐co‐chlorotrifluoroethylene) microstructures with tailored architecture, morphology, and wettability is presented. The patterned microstructures are fabricated using a simple, effective, low cost, and reproducible technique based on microfluidic technology. These novel structures can represent innovative platforms for advanced strategies in a wide range of biotechnological applications, including tissue engineering, drug delivery, microfluidic, and sensors and actuators devices. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1802–1810