A concise synthetic route from methylmalonate to a tetravalent aliphatic scaffold has been developed. The ensuing tetra-tethered derivative is equipped with two hydroxyl groups, as well as orthogonal alkene and alkyne functionalities. The usefulness of the scaffold has been demonstrated with the preparation of two representative multivalent derivatives: (i) a tetravalent compound containing two D-mannose units, one fluorescent boron-dipyrromethene (BODIPY) dye and a suitably functionalized amino acid and (ii) by way of dimerization and saponification, a water-soluble tetramannan derivative containing two fluorescent BODIPY units. Additionally, photophysical measurements conducted on these derivatives support the viability of the herein designed single and double BODIPY-labeled carbohydrate-based clusters as fluorescent markers. © 2019 by the authors.

Fluorescent difluoroboron dipyrromethenes (BODIPYs), have been accessed in a one-pot synthetic operation from phthalides and pyrroles, a process that involves O-ethylation of phthalides with Meerwein's reagent (Et 3 OBF 4 ) and reaction of the ensuing tetrafluoroborate salts with pyrrole, followed by treatment with BF 3 · OEt 2 . These derivatives are endowed with a ortho-hydroxymethyl 8-C-aryl group for further derivatization and/or conjugation to, among others, carbohydrates. The new conjugate derivatives benefit from the optimal characteristics of BODIPYs as fluorescent dyes, including in some instances water-solubility (in the case of conjugation to unprotected carbohydrates). The different kinds of BODIPY-carbohydrate derivatives are compounds of potential interest for biological studies. ©2019 IUPAC & De Gruyter. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. For more information, please visit: http://creativecommons.org/licenses/by-nc-nd/4.0/ 2019.

We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone + melatonin hybrids as potential agents for Alzheimer’s disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC50 = 11.90 ± 0.05 nM), moderate hAChE (IC50 = 1.73 ± 0.34 μM), hMAO A (IC50 = 2.78 ± 0.12 μM), and MAO B (IC50 = 21.29 ± 3.85 μM) inhibition, while keeping a strong antioxidant power (3.04 TE, ORAC test). Consequently, the results reported here support the development of new multitarget Donepezil + Chromone + Melatonin hybrids, such as compound 14n, as a potential drug for AD patients cure. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Goat colostrum is a rich source of carbohydrates, mainly constituted by lactose, although several minor bioactive oligosaccharides are also present. Analysis of these caprine milk oligosaccharides (COS) is not straightforward, and usually requires a previous fractionation step to remove lactose. In this work, a biotechnological fractionation methodology based on the use of a β-galactosidase from Kluyveromyces lactis was optimised (pH, incubation time, goat milk:enzyme volume ratio) to hydrolyse lactose, preserving the COS profile. Best results were obtained after 15 min of enzymatic treatment using 0.68 U mL −1 of enzyme at 37 °C and pH 7. Efficient removal of resulting monosaccharides was finally carried out by the incubation of these samples with Saccharomyces cerevisiae (37 °C, 24 h). Fractionation of these carbohydrates could help to better determine COS structures and to expand the applications of the purified COS in the food and pharmaceutical industries. © 2019 Elsevier Ltd

Oxidative cleavage (OsO 4 /NaIO 4 ) of a monoprotected dihydroxy sulfinyl diene affords a lactol, readily transformed into a sulfinyl pyranose. Alternatively, base promoted intramolecular cyclization of a lactol derived carbamate to a bicyclic oxazolidinone followed by simple transformations leads to an amino sulfonyl pyranose. In contrast, ozonolysis of a variety of hydroxy sulfinyl dienes leads to fair yields of 3-sulfinyl furans in a single step. © 2019 Elsevier Ltd

A regioselective synthesis of general applicability has been designed for the one-pot preparation of 2,3-disubstituted-cyclobutenones from iodoalkynes through cyclobutenylation, Suzuki CC coupling, and ketone formation. This one-pot methodology has been applied to the selective synthesis of an orally active cyclooxygenase II inhibitor. Furthermore, the obtained cyclobut-2-en-1-ones were used as synthons in several transformations, such as, the preparation of β-lactams, phthalazines, cyclohexa-2,5-dien-1-ones, and cyclopent-3-en-1-ones. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Bacterial multidrug resistance is becoming a growing problem for public health, due to the development and spreading of bacterial strains resistant to antimicrobials. In this study, the antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Enterococcus faecalis, Escherichia coli, and Chlamydia trachomatis D. The combination effect of compounds with antibiotics was examined by the minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA. Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results it can be concluded that this group of selenocompounds can be attractive potential antibacterials and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel selenocompounds, is of high impact in the fight against resistant pathogens. © 2019 by the authors.

Persistent organic pollutants (POPs) were assessed for the first time in blue whales from the South Pacific Ocean. Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane and its main metabolites (DDTs), were determined in 40 blubber samples from 36 free-ranging individuals and one stranded, dead animal along the coast of southern Chile between 2011 and 2013. PCBs were the most abundant pollutants (2.97–975 ng/g l.w.), followed by DDTs (3.50–537 ng/g l.w.), HCB (nd–77.5 ng/g l.w.) and PBDEs (nd–33.4 ng/g l.w). There was evidence of differences between sexes, with lower loads in females potentially due to pollutants passing to calves. POP concentrations were higher in specimens sampled in 2013; yet, between-year differences were only statistically significant for HCB and PBDEs. Lower chlorinated (penta > tetra > tri) and brominated (tetra > tri) congeners were the most prevalent among PCBs and PBDEs, respectively, mostly in agreement with findings previously reported in blue and other baleen whales. The present study provides evidence of lower levels of contamination by POPs in eastern South Pacific blue whales in comparison to those reported for the Northern Hemisphere. © 2018

Sugar alcohols, such as xylitol, sorbitol and inositols, are added-value carbohydrates with relevant bioactive and technological properties. These features make their extraction from natural sources of great interest both from the scientific and industrial points of view. However, due to the similarity of the chemical structures of the different carbohydrates and the complexity of the extracted mixtures, the subsequent isolation of these sugar alcohols from other coextracted low molecular weight carbohydrates (LMWC) is still considered a challenging task. In this article, the solubility of linear sugar alcohols and inositols in selected ionic liquids (ILs), i.e., 1-hexyl-3-methylimidazolium chloride ([HMIM][Cl]), 1-ethyl-3-methylimidazolium dicyanamide ([EMIM][DCA]), 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]) and 1,3-dimethylimidazolium dimethylphosphate ([MMIM][Me 2 PO 4 ]), has been investigated. The experimental results demonstrated widely divergent solubilities (in the 1.7–84.7\%, w/w, range) for the several targeted carbohydrates in the different ILs evaluated, with [EMIM][OAc] and [MMIM][Me 2 PO 4 ] providing the highest solubility values. These ILs gave also the best results when applied to the selective fractionation of sugar alcohols from other LMWC in 1:1 (w/w) binary mixtures (yields in the 60–98\% range). These results show ILs as promising non-volatile and environmental friendly solvents for this type of fractionation process and suggest the interest of further investigation in this particular application field. © 2018 Elsevier B.V.

Polysulfides (H2Sx) represent a class of reactive sulfur species (RSS) which includes molecules such as H2S2, H2S3, H2S4, and H2S5, and whose presence and impact in biological systems, when compared to other sulfur compounds, has only recently attracted the wider attention of researchers. Studies in this field have revealed a facet-rich chemistry and biological activity associated with such chemically simple, still unusual inorganic molecules. Despite their chemical simplicity, these inorganic species, as reductants and oxidants, metal binders, surfactant-like 'cork screws' for membranes, components of perthiol signalling and reservoirs for inorganic hydrogen sulfide (H2S), are at the centre of complicated formation and transformation pathways which affect numerous cellular processes. Starting from their chemistry, the hidden presence and various roles of polysulfides in biology may become more apparent, despite their lack of clear analytical fingerprints and often murky biochemical footprints. Indeed, the biological chemistry of H2Sx follows many unexplored paths and today, the relationship between H2S and its oxidized H2Sx species needs to be clarified as a matter of 'unmistaken identity'. Simultaneously, emerging species, such as HSSeSH and SenS8-n, also need to be considered in earnest. © 2019 by the authors.

We describe here the preparation, neuroprotective analysis, and antioxidant capacity of 11 novel quinolylnitrones (QN). The neuroprotective analysis of QN1-11 in an oxygen-glucose deprivation model, in primary neuronal cultures, has been determined, allowing us to identify QN6 as a very potent neuroprotective agent, showing significant high value at 0.5 and 10 μM (86.2\%), a result in good agreement with the observed strong hydroxyl radical scavenger of QN6. Copyright © 2019 American Chemical Society.

Multidrug efflux systems play a prominent role in medicine, as they are important contributors to bacterial antibiotic resistance. NorA is an efflux pump transporter from the major facilitator superfamily that expels numerous drug compounds across the inner membrane of Staphylococcus aureus (S. aureus). The design of novel inhibitors to combat drug efflux could offer new opportunities to avoid the problem of antibiotic resistance. In this study, we performed molecular modeling studies in an effort to discover novel NorA efflux pump inhibitors. A group of over 673 compounds from the PubChem database with a high (>80\%) level of similarity to the chemical structure of capsaicin was used to study the binding affinity of small molecule compounds for the NorA efflux pump. Ten potential lead compounds displayed a good druggability profile, with one in particular (CID 44330438) providing new insight into the molecular mechanism of the inhibition of major facilitator superfamily (MFS) efflux pump transporters. It is our hope that the overall strategy described in this study, and the structural information of the potential novel inhibitors thus identified, will stimulate others to pursue the development of better drugs to tackle multidrug resistance in S. aureus. © 2019, MDPI AG. All rights reserved.

We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 µM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC 50 (hAChE) = 22.0 ± 1.3 µM; IC 50 (hBuChE) = 6.79 ± 0.33 µM). Moreover, QT78 showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer’s disease. © 2019 by the authors.