Developing pyrrole-derived antimycobacterial agents: a rational lead optimization approach

Tuberculosis (TB) represents a never-ending challenge toward which research efforts are needed. Drug resistance is the key problem that scientists in the field need to fight. The development of new drugs endowed with novel modes of action against different biological targets is of extreme importance; these new agents should also exhibit lower toxicity compared with the anti-TB drugs currently available. Furthermore, new drugs should be inexpensive since most of the TB-infected population lives in developing nations. In the last few years, numerous researchers have focused their attention on TB, leading to the discovery of some interesting compounds. Among these, the pyrrole-derived compounds we developed can be considered very promising antimycobacterial agents. Aided by molecular modeling studies, we synthesized numerous compounds characterized by the same 1,5-diarylpyrrole scaffold and elucidated very interesting antitubercular/antimycobacterial properties. Some compounds identified are extremely promising and represent a step towards the design of novel lead structures in the fight against TB. Our efforts to this end are reviewed here.     

Thermal,thermo‐mechanical,and dynamic mechanical properties of polypropylene/cycloolefin copolymer blends

Interaction of the components and physical properties of the polypropylene (PP)/cycloolefin copolymer (COC) blends were studied by means of differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA), Vicat softening temperature (VST), and measurements of the coefficient of linear thermal expansion (CLTE) and of the density. The attention was focused on the blends with 90–60% of PP by wt, where the COC minority component was present in the form of short fibers. DSC, DMTA, and density measurements concurrently prove the immiscibility of PP and COC. DSC measurements reveal that crystallinity and melting temperature of the PP component slightly decrease with the fraction of COC in blends, in the range of 56–47% and 164–161°C, respectively. Storage modulus and loss modulus of the blends are in a good accord with the model predictions based on (i) the equivalent box model (EBM) and on (ii) modified equations of the percolation theory. The dependence of the VST on the blend composition is in a good correlation with the previous morphological analysis. Measurements of the coefficient of thermal expansion provide useful data as the functions of temperature and blend composition. Density of the blends was found to obey the volume additivity. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

Synthesis, Molecular Characterization and Preliminary Antioxidant Activity Evaluation of Quercetin Fatty Esters

Quercetin shows interesting pharmacological effects, but its use in topical applications is limited by its low skin permeability and solubility. In this work, the synthesis of highly lipophilic quercetin esters with oleic, linoleic and linolenic acid useful as topical quercetin prodrugs is reported. Partial OH esterification is advisable to maintain the antioxidant activity of these compounds; tetraesters and triesters can be achieved by modulating the reaction conditions utilized for the total esterification of quercetin. The chemical structures of the esters were proven by spectroscopic techniques; quantum chemical NMR calculation were mandatory to unequivocally assign the free position in triesters. Finally, the antioxidant activity of all the synthesized compounds was determined by the 2,2-diphenyl-1-picryl-hydrazyl method and by 2,2-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) assay.     

GAS-LIQUID REACTORS WITH VOLATILE LIQUID REACTANTS: APPROXIMATE SOLUTION FOR CONSECUTIVE BIMOLECULAR REACTIONS OF GENERAL ORDER

An approximate solution of the film model in presence of volatile liquid reactants is presented for the case of a general van de Vusse-like reaction scheme and general power-law reaction rates. The solution is obtained in a closed-form and simply requires the numerical solution of a system of nonlinear equations. The developed approximate solution is valid for any reaction regime and any number of reactions taking place within the liquid him. The application to a CSTR is discussed; this also serves as a test of the accuracy of the approximate solution carried out by comparison with the complete film model solved via the orthogonal collocation method. The numerical studies show that the approximate solution can be used with confidence for the usual encountered rate laws and that the volatility of the liquid reactants affects the performance of the CSTR mostly at the intermediate value of the Halt a number.     

Oxygen Storage Behavior of Ceria–Zirconia-Based Catalysts in the Presence of SO2

This paper investigates the effect of the presence of SO₂ in the dynamics of oxygen storage on ceria and ceria–zirconia. The introduction of SO₂ under reaction conditions at T<873 K negatively affects CO conversion under oscillating conditions on all the supports studied, owing to the formation of sulfate species. Deactivation is observed on all supports and activity is recovered only after desorption of SO₂, which occurs at 950<T<1000 K, depending on catalyst composition (Ce/Zr ratio) and treatment atmosphere. The amount of sulfur adsorbed is higher over solid solutions, reaching a maximum with Ce _x Zr_1–x O₂ (0.5<x<0.68). However this does not adversely affect activity compared to ceria. In the presence of Rh and Pd, reactivation is favored under reaction conditions. More generally, it appears that the removal of sulfates is facilitated in reductive atmospheres (both hydrogen and CO) over mixed oxides. No differences are observed following regeneration under oxidizing conditions.     

Synthesis,Computational Studies and Assessment of in Vitro Activity of Squalene Derivatives as Carbonic Anhydrase Inhibitors

We report novel molecules incorporating the nontoxic squalene scaffold and different carbonic anhydrase inhibitors (CAIs). Potent inhibitory action, in the low-nanomolar range, was detected against isoforms hCA II for sulfonamide derivatives, which proved to be selective against this isoform over the tumor-associate hCA IX and XII isoforms. On the other hand, coumarin derivatives showed weak potency but high selectivity against the tumor-associated isoform CA IX. These compounds are interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. In addition, an in silico study of inhibitor-bound hCA II revealed extensive interactions with the hydrophobic pocket of the active site and provided molecular insights into the binding properties of these new inhibitors.     

Pectin: A Long-Neglected Broad-Spectrum Antibacterial

First reported in the late 1930s and partly explained in 1970, the antibacterial activity of pectin remained almost ignored until the late 1990s. The concomitant emergence of research on natural antibacterials and new usages of pectin polysaccharides, including those in medicine widely researched in Russia, has led to a renaissance of research into the physiological properties of this uniquely versatile polysaccharide ubiquitous in plants and fruits. By collecting scattered information, this study provides an updated overview of the subtle factors affecting the behaviour of pectin as an antimicrobial. Less-degraded pectin extracted by acid-free routes, we argue in the conclusions, will soon find applications from new treatments for polymicrobial infections to use as an implantable biomaterial in tissue and bone engineering.     

Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review

Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.     

Extraction of phenolic compounds from Vitex agnus-castus L.

The primary objective of this study was to valorized Vitex agnus-castus residues in terms of phenolic compounds. The effects of extraction time (30–360 min), solid to liquid ratio (0.1–0.3 g_DryBiomass/ml_Solvent), type of solvent and different tissue types (leave, roots and seeds) on total polyphenols, o-diphenols, total flavonoids and anthocyanins were evaluated. The highest total polyphenol (31.5 mg_{CaffeicAcidEquivalent}/g_DryBiomass) and o-diphenol (12.4 mg_{CaffeicAcidEquivalent}/g_DryBiomass) contents were obtained from methanolic extract of leaves after 180 min using a solid/liquid ratio of 0.1 g_DryBiomass/ml_Solvent, while total flavonoids, reached a maximum value of 19.4 mg_{CatechinEquivalent}/g_DryBiomass after 360 min under the same conditions. Roots of V. agnus-castus were found to be a good source of anthocyanins with the highest yield of 0.62 mg_{MalvidinEquivalent}/g_DryBiomass using ethanol as a solvent (180 min and 0.2 g_DryBiomass/ml_Solvent). The maximum antiradical power (178.5 μl_extract/μg_DPPH) was exhibited by the methanolic leave extract obtained after 360 min at solid/liquid ratio of 0.3 g_DryBiomass/ml_Solvent.     

Urethanes and polyurethanes based on oxypropylated cork: 1. Appraisal and reactivity of products

The reaction of various polyols derived from the oxypropylation of cork with aliphatic and aromatic mono‐ and diisocyanates was studied in solution at room temperature. In all instances, good second‐order kinetics were observed and the corresponding rate constant determined. The reactivity of the aromatic isocyanate was found to be much higher than that of aliphatic counterparts. The ensuing urethanes and polyurethanes were characterised by FTIR and ¹H NMR spectroscopy, DSC and sol/gel distribution. © 2001 Society of Chemical Industry