Asymmetric Synthesis of Highly Enantiomerically Enriched (S)(-)-β-Bisabolene

(S)-β-Bisabolene, (S)-1, was synthetized by a synthetic route in which (S)-4-methyl-3-cyclohexene carboxylic acid, (S)-10, which was the key intermediate, was prepared via a highly diastereoselective TiCl₄-catalyzed Diels-Alder reaction between isoprene and the acrylate of commercial (R)-pantolactone, followed by hydrolysis. Compound (S)-10 was then converted into ketone (S)-13 using two different procedures. The best one of these, as regards the degree of stereospecificity, involved the reaction of (S)-10 with 2 equiv of 4-methyl-3-penten-1-yllithium, 14, in the presence of CeCl₃, and gave (S)-13 having ca. 84% ee. The Zr-promoted methylenation of this ketone afforded highly enantiomerically enriched (S)-1.     

Unusual Inherent Electrochemistry of Graphene Oxides Prepared Using Permanganate Oxidants

Graphene and graphene oxides are materials of significant interest in electrochemical devices such as supercapacitors, batteries, fuel cells, and sensors. Graphene oxides and reduced graphenes are typically prepared by oxidizing graphite in strong mineral acid mixtures with chlorate (Staudenmaier, Hofmann) or permanganate (Hummers, Tour) oxidants. Herein, we reveal that graphene oxides pose inherent electrochemistry, that is, they can be oxidized or reduced at relatively mild potentials (within the range ±1 V) that are lower than typical battery potentials. This inherent electrochemistry of graphene differs dramatically from that of the used oxidants. Graphene oxides prepared using chlorate exhibit chemically irreversible reductions, whereas graphene oxides prepared through permanganate‐based methods exhibit very unusual inherent chemically reversible electrochemistry of oxygen‐containing groups. Insight into the electrochemical behaviour was obtained through cyclic voltammetry, chronoamperometry, and X‐ray photoelectron spectroscopy experiments. Our findings are of extreme importance for the electrochemistry community as they reveal that electrode materials undergo cyclic changes in charge/discharge cycles, which has strong implications for energy‐storage and sensing devices.     

Synthesis of 3-iodothiophenes via iodocyclization of (Z)-thiobutenynes

A simple synthesis of 3-iodothiophenes was demonstrated using a wide range of (Z)-thioenynes. The key step in the iodocyclofunctionalization was the selective reduction of the triple bond in (Z)-thioenynes by the addition of iodine as an electrophilic agent. The 3-iodothiophenes were obtained in good to excellent yields of 61–92%. The 3-iodothiophenes were used as substrates in Sonogashira cross-coupling reactions to obtain thiophene acetylenes.     

Lipid-Based Nanostructures for the Delivery of Natural Antimicrobials

Encapsulation can be a suitable strategy to protect natural antimicrobial substances against some harsh conditions of processing and storage and to provide efficient formulations for antimicrobial delivery. Lipid-based nanostructures, including liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid nanocarriers (NLCs), are valuable systems for the delivery and controlled release of natural antimicrobial substances. These nanostructures have been used as carriers for bacteriocins and other antimicrobial peptides, antimicrobial enzymes, essential oils, and antimicrobial phytochemicals. Most studies are conducted with liposomes, although the potential of SLNs and NLCs as antimicrobial nanocarriers is not yet fully established. Some studies reveal that lipid-based formulations can be used for co-encapsulation of natural antimicrobials, improving their potential to control microbial pathogens.     

Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening,Biochemical Evaluation and Molecular Modeling Studies

Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. The most active compound, (E)-2-O-farnesyl chalcone, decreased the rate of oxygen consumption to an extent similar to that of the positive control, nordihydroguaiaretic acid. Additionally, studies on the mechanism of the action indicated that (E)-2-O-farnesyl chalcone is a competitive LOX-1 inhibitor. Molecular modeling studies indicated the importance of the prenyl moieties for the binding of the inhibitors to the LOX binding site, which is related to their pharmacological properties.     

Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy

Plant-based foods, like fruits, vegetables, whole grains, legumes, nuts, seeds and other foodstuffs, have been deemed as heart healthy. The chemicals within these plant-based foods, i.e., phytochemicals, are credited with protecting the heart. However, the mechanistic actions of phytochemicals, which prevent clinical endpoints, such as pathological cardiac hypertrophy, are still being elucidated. We sought to characterize the overlapping and divergent mechanisms by which 18 selected phytochemicals prevent phenylephrine- and phorbol 12-myristate 13-acetate-mediated cardiomyocyte enlargement. Of the tested 18 compounds, six attenuated PE- and PMA-mediated enlargement of neonatal rat ventricular myocytes. Cell viability assays showed that apigenin, baicalein, berberine hydrochloride, emodin, luteolin and quercetin dihydrate did not reduce cell size through cytotoxicity. Four of the six phytochemicals, apigenin, baicalein, berberine hydrochloride and emodin, robustly inhibited stress-induced hypertrophy and were analyzed further against intracellular signaling and genome-wide changes in mRNA expression. The four phytochemicals differentially regulated mitogen-activated protein kinases and protein kinase D. RNA-sequencing further showed divergence in gene regulation, while pathway analysis demonstrated overlap in the regulation of inflammatory pathways. Combined, this study provided a comprehensive analysis of cardioprotective phytochemicals. These data highlight two defining observations: (1) that these compounds predominantly target divergent gene pathways within cardiac myocytes and (2) that regulation of overlapping signaling and gene pathways may be of particular importance for the anti-hypertrophic actions of these phytochemicals. Despite these new findings, future works investigating rodent models of heart failure are still needed to understand the roles for these compounds in the heart.     

Chemical Antibody Mimics Inhibit Cadherin-Mediated Cell–Cell Adhesion: A Promising Strategy for Cancer Therapy

One of the most promising strategies to treat cancer is the use of therapeutic antibodies that disrupt cell–cell adhesion mediated by dysregulated cadherins. The principal site where cell–cell adhesion occurs encompasses Trp2 found at the N-terminal region of the protein. Herein, we employed the naturally exposed highly conserved peptide Asp1-Trp2-Val3-Ile4-Pro5-Pro6-Ile7, as epitope to prepare molecularly imprinted polymer nanoparticles (MIP-NPs) to recognize cadherins. Since MIP-NPs target the site responsible for adhesion, they were more potent than commercially available therapeutic antibodies for inhibiting cell–cell adhesion in cell aggregation assays, and for completely disrupting three-dimensional tumor spheroids as well as inhibiting invasion of HeLa cells. These biocompatible supramolecular anti-adhesives may potentially be used as immunotherapeutic or sensitizing agents to enhance antitumor effects of chemotherapy.     

3D printing for aqueous and non-aqueous redox flow batteries

Additive manufacturing technologies, generally grouped under the name of 3D printing, are experiencing an explosion of interest during the last few years. The possibility of fast prototyping enabled by 3D printing has been recognized as a crucial booster for device fabrication and general scientific advancements. In this review, attention is focused on the latest developments in the field of redox flow batteries which are, similar to other energy related devices, characterized by the recent adoption of 3D printing methods for the fabrication of key components. Whether simply to investigate flow phenomena, test new designs or fabricate final-product components with custom features, the use of 3D printing can critically drive this field of research towards better performing energy-storage systems. The latest and most representative examples of redox flow battery studies will be discussed, categorized in relation to the electrolyte used and whether the devices are employed in aqueous or non-aqueous applications.     

Theoretical optimization of Irinotecan-based anticancer strategies in the case of drug-induced efflux

The anticancer drug Irinotecan (CPT11) is known to trigger the induction of ATP-Binding Cassette (ABC) transporters, responsible for the efflux of the drug and its metabolites outside of the cells. The drug-modulated overexpression of those transporters prevents its accumulation in the intracellular medium, therefore decreasing its efficacy. A critical clinical concern lies in the design of CPT11-based therapeutic strategies which eradicate a maximum number of cancer cells despite their ability to become resistant. In order to address this issue, we supplemented an existing mathematical model of CPT11 molecular pharmacokinetics–pharmacodynamics (PK–PD) with a new model of CPT11-induced overexpression of ABC transporters. We then theoretically optimized exposure to CPT11 given as a single agent or combined either with ABC transporter inhibitors, or with inhibitors of nuclear factors whose activation is responsible for transporter overexpression. We firstly considered a cancer cell population endowed with the ability of inducing their transporters. For any drug combination, we concluded that the highest concentration of CPT11 should be administered in order to kill a maximum number of cancer cells, despite the triggering of resistance. We then considered a population of healthy cells which were assumed to be identical to cancer cells except that they were not able to become resistant. Optimal schemes were defined as the ones which maximized DNA damage in cancer cells under the constraint of DNA damage in healthy cells not exceeding a tolerability threshold. The optimal therapeutic strategy consisted in combining CPT11 with ABC transporter inhibitors as it achieved a complete reversal of resistance by means of the lowest concentrations of CPT11.