Glycans in Medicinal Chemistry: An Underexploited Resource

The biological relevance of glycans as mediators of key physiological processes, including disease‐related mechanisms, makes them attractive targets for a wide range of medical applications. Despite their important biological roles, especially as molecular recognition elements, carbohydrates have not been fully exploited as therapeutics mainly due to the scarcity of structure–activity correlations and their non‐drug‐like properties. A more detailed understanding of the complex carbohydrate structures and their associated functions should contribute to the development of new glycan‐based pharmaceuticals. Recent significant progress in oligosaccharide synthesis and chemical glycobiology has renewed the interest of the medicinal chemistry community in carbohydrates. This promises to increase our possibilities to harness them in drug discovery efforts for the development of new and more effective, synthetic glycan‐based therapeutics and vaccines.     

Intelligent micellar polymeric nanocarriers for therapeutics and diagnosis

Polymeric micelles can be designed and synthesized to bear polymeric blocks with different hydrophilicities; this triggers their self‐assembly into micellar aggregates similar to those generated with traditional surfactants. The basic structure consists of a hydrophobic core, capable of containing guest substances, and a hydrophilic shell, which stabilizes the payload and protects it from external degradation or prevents its quick elimination from the body. The accumulation of block copolymer micelles (BCMs) in a target cell or tissue can be accomplished by two main mechanisms, passive and active targeting; this allows the payload release at the site of action when desired. Hence, in this general overview, we pay special attention to newly developed single‐stimulus‐ and multi‐stimuli‐responsive delivery systems capable of disassembling and reassembling (in some cases) as a response to changes in their physicochemical properties. Also, special interest is also devoted to multifunctional BCMs incorporating multiple therapeutic agents and/or multiple imaging contrast agents, which can be considered the new generation (third generation) of drug‐delivery systems, that is, nanotheranostic platforms. Finally, a summary of BCM‐based drug‐delivery systems currently under clinical trials is given. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42650.     

Ile-1781-Leu and Asp-2078-Gly Mutations in ACCase Gene,Endow Cross-resistance to APP,CHD, and PPZ in Phalaris minor from Mexico

Herbicides that inhibit acetyl coenzyme A carboxylase (ACCase) are commonly used in Mexico to control weedy grasses such as little seed canarygrass (Phalaris minor). These herbicides are classified into three major families (ariloxyphenoxypropionates (APP), cyclohexanodiones (CHD), and, recently, phenylpyrazolines (PPZ)). In this work, the resistance to ACCase (APP, CHD, and PPZ) inhibiting herbicides was studied in a biotype of Phalaris minor (P. minor) from Mexico, by carrying out bioassays at the whole-plant level and investigating the mechanism behind this resistance. Dose-response and ACCase in vitro activity assays showed cross-resistance to all ACCase herbicides used. There was no difference in the absorption, translocation, and metabolism of the ¹⁴C-diclofop-methyl between the R and S biotypes. The PCR generated CT domain fragments of ACCase from the R biotype and an S reference were sequenced and compared. The Ile-1781-Leu and Asp-2078-Gly point mutations were identified. These mutations could explain the loss of affinity for ACCase by the ACCase-inhibing herbicides. This is the first report showing that this substitution confers resistance to APP, CHD, and PPZ herbicides in P. minor from Mexico. The mutations have been described previously only in a few cases; however, this is the first study reporting on a pattern of cross-resistance with these mutations in P. minor. The findings could be useful for better management of resistant biotypes carrying similar mutations.     

Crossing Paths in Human Renal Cell Carcinoma (hRCC)

Historically, cell-signaling pathways have been studied as the compilation of isolated elements into a unique cascade that transmits extracellular stimuli to the tumor cell nucleus. Today, growing evidence supports the fact that intracellular drivers of tumor progression do not flow in a single linear pathway, but disseminate into multiple intracellular pathways. An improved understanding of the complexity of cancer depends on the elucidation of the underlying regulatory networks at the cellular and intercellular levels and in their temporal dimension. The high complexity of the intracellular cascades causes the complete inhibition of the growth of one tumor cell to be very unlikely, except in cases in which the so-called “oncogene addiction” is known to be a clear trigger for tumor catastrophe, such as in the case of gastrointestinal stromal tumors or chronic myeloid leukemia. In other words, the separation and isolation of the driver from the passengers is required to improve accuracy in cancer treatment. This review will summarize the signaling pathway crossroads that govern renal cell carcinoma proliferation and the emerging understanding of how these pathways facilitate tumor escape. We outline the available evidence supporting the putative links between different signaling pathways and how they may influence tumor proliferation, differentiation, apoptosis, angiogenesis, metabolism and invasiveness. The conclusion is that tumor cells may generate their own crossroads/crosstalk among signaling pathways, thereby reducing their dependence on stimulation of their physiologic pathways.     

Direct Extraction of Propionic Acid from Propionibacterium acidipropionici Broths with Tri‐n‐octylamine

The direct reactive extraction of propionic acid from Propionibacterium acidipropionici broths with solutions of tri‐n‐octylamine in dichloromethane, n‐butyl acetate or n‐heptane underlined the strong negative influence of the cells, due to the blockage of the interface by their adsorption. The magnitude of this effect <#>depends on the affinity of the cells for the organic phase, which is more important for n‐heptane, but only at biomass concentrations below 18 g L^–1 d.w. (dry weight). Moreover, the interfacial mass transfer of the acid is also controlled by the solvent polarity, and is accelerated from n‐heptane to dichloromethane and by the addition to the organic phase of 1‐octanol as a phase modifier. The influences of the biomass concentration, the rotation speed and the solvent dielectric constant were included in a mathematical model describing the solute mass flow from the aqueous to the organic phase.     

Removal of sulfamethoxazole from waters and wastewaters by conductive‐diamond electrochemical oxidation

BACKGROUND: Sulfamethoxazole (SMX, used as a model bacteriostatic antibiotic) is persistent to conventional biological treatments of wastewaters. In this work, conductive‐diamond electrochemical oxidation (CDEO) was found to be an effective technology for its removal from the effluents of conventional wastewater treatment plants. RESULTS: The use of CDEO has been evaluated for the removal of the antibiotic SMX from water and wastewaters. The results show that CDEO can reduce the concentration of this organic pollutant to values below 0.1 µg dm^?3. The variation of the SMX concentration during electrolysis shows a complex shape with a plateau zone that increases in size with the initial concentration of SMX. This complex trend is not observed in the changes of TOC, which seems to indicate that the CDEO of SMX solutions does not lead directly to the generation of carbon dioxide as a final product. A tentative reaction pathway has been proposed based on a thorough analysis of the reaction mixture, in which the main intermediate products were identified. The use of liquid chromatography time‐of‐flight mass spectrometry (LC‐TOFMS) allowed the identification of nine organic intermediates (with M_w 98, 108, 172, 173, 197, 203, 227, 269 and 287) during the electrolysis and the concentration of these compounds depends on the initial SMX concentration and on the current density applied. CONCLUSIONS: CDEO is able to reduce the concentration of the organic pollutant below 0.1 mg dm^?3. SMX removal is faster than that of TOC. This fact indicates the formation of reaction intermediates. Analytical techniques show that nine reaction intermediates are generated in the system, and that their concentration depends on the initial SMX concentration and on the current density used. Copyright © 2012 Society of Chemical Industry     

The Composition of Mixed Micelles Formed by Dodecyl Trimethyl Ammonium Bromide and Benzethonium Chloride in Water

The composition of the mixed micelles formed by benzethonium chloride and dodecyl trimethyl ammonium bromide in water were experimentally determined by a combination of surfactant ion-selective electrodes and UV–Vis spectroscopy measurements. Results were compared with the computed compositions from three theories on mixed micelles available in the literature (Regular Solution, Motomura’ and Georgiev’s). The basis of the Junquera and Aicart method and the determination of the micelle aggregation number (N) by pyrene fluorescence quenching, i.e., the constancy of N and the mixed micelle composition when the total concentration is changed, were not supported by our experimental results. Experimental micelle compositions were statistically equal to those computed by Regular Solution Theory. The mixed micelle composition and the quantity of non-micellized surfactant molecules change with concentration above the critical micelle concentration, and therefore do not support the assumptions used in the Junquera and Aicart procedure and in the determination of N by pyrene fluorescence quenching. The reason why the latter procedure gives N values similar to those obtained from other techniques is discussed.     

Cr(VI) removal from synthetic and real wastewaters: The use of the invasive biomass Sargassum muticum in batch and column experiments

The macroalgae Sargassum muticum was selected for the treatment of solutions containing Cr(VI). Very acidic pH values were established as optimal for Cr(VI) reduction. Algae chemical modification reduced equilibrium time to 4 h. First order kinetic model was used to describe the reduction kinetic of Cr(VI). A column experiment allowed to distinguish the processes occurring during Cr(VI) elimination: its reduction to Cr(III) and the subsequent adsorption of this species formed. Under the selected conditions the biomass was capable of reducing all the incoming Cr(VI) during 77 h. Industrial wastewaters from chrome plating industry were also tested for chromium removal.     

Noncanonical Reactions of Flavoenzymes

Enzymes containing flavin cofactors are predominantly involved in redox reactions in numerous cellular processes where the protein environment modulates the chemical reactivity of the flavin to either transfer one or two electrons. Some flavoenzymes catalyze reactions with no net redox change. In these reactions, the protein environment modulates the reactivity of the flavin to perform novel chemistries. Recent mechanistic and structural data supporting novel flavin functionalities in reactions catalyzed by chorismate synthase, type II isopentenyl diphosphate isomerase, UDP-galactopyranose mutase, and alkyl-dihydroxyacetonephosphate synthase are presented in this review. In these enzymes, the flavin plays either a direct role in acid/base reactions or as a nucleophile or electrophile. In addition, the flavin cofactor is proposed to function as a “molecular scaffold” in the formation of UDP-galactofuranose and alkyl-dihydroxyacetonephosphate by forming a covalent adduct with reaction intermediates.     

Screening of lactic acid bacteria for fermentation of minced wastes of Argentinean hake (Merluccius hubbsi)

Sixteen strains of lactic acid bacteria were evaluated for their capacity of acidification of Merluccius hubbsi fish wastes obtained from a processing factory. Only three lactobacilli (Lactobacillus buchneri B-1837, Lactobacillus arizonensis B-14768 and Lactobacillus plantarum B-4496) were able to reduce the pH value to 4.0 or below when using glucose or sucrose as carbon source. Either with only 25 g l^?1 of glucose or sucrose, L. arizonensis B-14768 reduced the pH to 3.8 ± 0.2 within 24 h of fermentation. The acid tolerance test (pH 3.0 at 37 °C) for the strains presented D_pH3-values of 192, 383 and 767 min for L. buchneri, L. plantarum and L. arizonensis, respectively. However, at a lower pH value (pH 2.0) only L. arizonensis was significantly recovered after 45 min of exposure (D_pH2 68 min). Considering together the acidification capacity, the tolerance to other stresses (heat and bile salts) and the lower optimum temperature for the process, L. arizonensis is described as a suitable strain for M. hubbsi silage; constituting a promissory alternative for fish fermentation at location with temperate or cold climes.