Butyltin(IV) Benzoates: Inhibition of Thioredoxin Reductase,Tumor Cell Growth Inhibition,and Interactions with Proteins

Thioredoxin reductase (TrxR) is overexpressed in cancer cells and is therefore a putative cancer target. Inhibition of this enzyme is considered an important strategy for the development of new chemotherapeutic agents with a specific mechanism of action. Organotin compounds have been described as experimental antitumor agents, yet their mechanism of action remains largely unknown. Based on the outcome of a virtual screening study, various di‐ and tri‐n‐butyltin(IV) carboxylates were synthesized, and their biological properties were evaluated. All synthesized compounds were able to inhibit TrxR selectively within the micromolar range and showed potent antitumor activity against HT‐29 and MCF‐7 cancer cell lines. Moreover, tin(IV) organometallics were found to strongly induce apoptosis in the BJAB lymphoma cell line. Mass spectrometry and atomic absorption spectroscopy experiments revealed metal binding to proteins, and efficient cellular uptake was observed using a di‐n‐butyltin(IV) complex as an example.     

Hybrid MCM-41 grafted by a general microwave-assisted procedure: a characterization study

Hybrid materials obtained through a Microwave-assisted grafting of organic functional groups on mesoporous silica (MCM-41 type) have been characterized by X-ray powder diffraction, TG-DSC, N₂ adsorption, solid state ¹³C- and ²⁹Si-NMR, TEM and SEM. The studied grafting procedure is effective in the preparation of hybrid organosilicas under solvent-free conditions. Microwaves allows an ultra-fast and clean functionalization of the mesoporous materials and the method has been applied to produce a wide series of functional materials. The hybrid materials maintain the original mesoporous structure when the loading of linked organic groups does not exceed 10 %. In this cases, the slight pore volume reduction is linearly correlated to the organic amount in the product. If functional groups able to interact among them through hydrogen bond are used, hybrid materials exhibit high Organic/SiO₂ ratios and low pore volumes due to the formation of a network occluding the pores, where functional groups of free organosilane molecules interacts with the functional groups of molecules linked to the matrix. NMR data confirm that the network is composed by organosilane molecules linked or not to the framework. Acid washing is able to labilize hydrogen bond and open the network. In the case of bulky but chemically inert functionalising agents the network is not produced.     

β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and ¹H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC_50s and EC_90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.     

Direct Regio‐, Diastereo‐, and Enantioselective Vinylogous Michael Addition of Prochiral 3‐Alkylideneoxindoles to Nitroolefins

3‐Alkylidene‐2‐oxindoles represent a simple, yet enabling subfamily of indole alkaloids, and their ability to react as electron‐poor acceptors has largely been investigated. In contrast, their utility as pronucleophilic synthons remains elusive. In this context, the present article describes the successful execution of the direct, organocatalytic asymmetric Michael addition of prochiral 3‐alkylideneoxindoles to nitroolefins. A variety of γ‐substituted alkylideneoxindoles carrying two stereocenters at both the γ‐ and δ‐carbon sites was assembled with excellent stereoselectivity and without olefin isomerization or stereochemical ablation.     

Reactively Modified Poly(lactic acid): Properties and Foam Processing

Summary: In order to produce modified poly(lactic acid) (PLA) resins for applications requiring high melt viscosity and elasticity (e.g., low‐density foaming, thermoforming), a commercial PLA product has been reactively modified in melt by sequentially adding 1,4‐butanediol and 1,4‐butane diisocyanate as low‐molecular‐weight chain extenders. By varying amounts of the two chain extenders associated to the end group contents of PLA, three resulted samples were obtained. They were then structurally characterized by FTIR spectroscopy and molecular structure analysis. Their thermal, dynamic mechanical thermal properties and melt viscoelastic properties were investigated and compared along with unmodified PLA. The results indicated that chemical modification may be characterized as chain scission, extension, crosslinking, or any combination of the three depending on the chain extender amounts. The increase of PLA molecular weight could be obtained by properly controlling amounts of two chain extenders. The samples with increased molecular weights showed enhanced melt viscosity and elasticity. Such property improvements promised a successful application for modified PLA in a batch foam processing by producing foams with reduced cell size, increased cell density and lowered bulk foam density in comparison with plain PLA foam.

Cellular morphology of a modified PLA foam.     

Alder ene functionalization of polyisobutene oligomer and styrene-butadiene-styrene triblock copolymer

The Alder ene functionalization reaction of double bonds containing macromolecules such as polyisobutene oligomer (PIB) and a styrene-butadiene-styrene triblock copolymer (SBS) samples with maleic anhydride (MAH) or diethyl maleate (DEM) as enophiles is described. The analysis of the products by means of different techniques assesses the addition of the polar molecules to the reactive vinylidene units of the polymer with functional degrees (FD) depending on the type of enophile and polymer reactivity. The role of the reaction conditions and the use as Lewis acids as catalysts are discussed in terms of their influence on the addition reaction extent and on the polymer molecular weight.     

Application of the dry‐spinning method to produce poly(ε‐caprolactone) fibers containing bovine serum albumin laden gelatin nanoparticles

We designed and manufactured a polymeric system with combined hydrophilic–hydrophobic properties by loading gelatin nanoparticles (GNPs) containing bovine serum albumin (BSA) into poly(ε‐caprolactone) (PCL) fibers. Our ultimate goal was to create a device capable of carrying and releasing protein drugs. Such a system could find several biomedical applications, such as those in controlled release systems, surgical sutures, and bioactive scaffolds for tissue engineering. A two‐step desolvation method was used to produce GNPs, whereas PCL fibers were produced by a dry‐spinning method. The morphological, mechanical, and thermal properties of the produced system were investigated, and the distribution of nanoparticles both inside and on the surface of the fibers was examined. The effect of the particles on the biodegradability of the fibers was also evaluated. In vitro preliminary tests were performed to study the release of BSA from nanoparticle‐laden fibers and to compare this with its release from free nanoparticles. Our results indicate that the distribution of particles inside the fibers was quite homogeneous and only a few of them were present on the surface. The presence of the particles in the fibers did not affect the thermal properties of the PCL polymer matrix, although it created voids that affected the degradation characteristics so the PCL fibers favored faster erosion compared to the plain fibers. Preliminary results indicate that the release from GNP‐laden fibers occurred much more slowly compared to that in the free GNPs. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44233.     

Effect of polypropylene morphology on thermal cis-trans isomerization and photofading of some azo dyes: A kinetic study

Five polypropylene films were prepared having different crystallinity and morphology, the latter having been modified by stretching. They were colored with azo dyes XC₆H₄N?NC₆H₄N(C₂H₅)₂ (where X?H, OCH₃, CN, and NO₂). The kinetics of the thermal cis-trans isomerization of these dyes has been studied in the range 21–41°C, much above the glass transition temperature of the polymer. The isomerization process was found to be strictly first-order; the kinetic parameter values have been correlated with the free volume extent in the amorphous regions of the matrix. Lightfastness of the dyes in the polymer matrices has been also investigated: It appeared to be more important for the unoriented samples with respect to the stretched ones and substantially independent on the crystalinity degree.     

Rationally designed inhibitors as tools for comparing the mechanism of squalene-hopene cyclase with oxidosqualene cyclase

The inhibition of squalene-hopene cyclase (SHC) (E.C. 5.4.99.-), an enzyme of bacterial membranes catalyzing the formation of pentacyclic sterol-like triterpenes, was studied by using different classes of compounds originally developed as inhibitors of oxidosqualene cyclase (OCS) (E.C. 5.4.99.7), the enzyme of eukaryotes responsible for the formation of tetracyclic precursors of sterols. The mechanism of cyclization of squalene by SHC, beginning with a protonation of the 2,3 double bond by an acidic residue of the enzyme, followed by a series of electrophilic additions of the carbocationic intermediates to the double bonds, is similar to the mechanism of cyclization of 2,3-oxidosqualene by OSC. The inhibitors studied included: (i) analogs of the carbocationic intermediates formed during cyclization, such as aza-analogs of squalene and 2,3-oxidosqualene; (ii) affinity-labeling inhibitors bearing a methylidene reactive group; and (iii) vinyldioxidosqualenes and vinylsulfide derivatives of the substrates. Comparison of the results obtained with the two enzymes, SHC and OSC, showed that many of the most effective inhibitors of OSC were also able to inhibit SHC, while some derivatives acted as specific inhibitors. Differences could be easily explained on the basis of the different substrate specificity of the two enzymes.