Identifying the factors that underlie signal divergences remains challenging in studies of animal communication. Regarding the chemical signalling, different compounds can be found in some species but be absent in others. We hypothesized that if the costs that are associated with the expression of some compounds are too high, their presence in the signal may be restricted. However, these compounds may be expressed and be functional when those costs are relaxed. Vitamin E (α-tocopherol), a dietary compound with metabolic relevancy, acts as an honest chemical sexual signal in many lizards but no in others such as the Carpetan Rock lizard (Iberolacerta cyreni). We investigated whether dietary supplementation favours the expression of this vitamin in scents of I. cyreni. We show that dietary constraints can preclude the expression of vitamin E in chemical secretions of wild males because was expressed when it was experimentally provided in the diet. Vitamin E supplementation also heightened the immune response of males and increased the interest of their scent for females, highlighting the vitamin E as a chemical sexual signal in this species. We suggest that diet could decisively act as a driver of intra-A nd interspecific divergences in the chemical signalling of lizards. © 2017 The Author(s).

Aim and Objective: Selenium (Se) compounds are often associated with good reactivity and selectivity due to specific modifications of thiol groups in peptides, proteins and enzymes. Among them, selenazolinium salts are of particular interest, as they react readily with their thiol targets. This study was undertaken to verify whether this reactivity translates into biological activity against a few selected organisms. Materials and Methods: To screen the activity of selenazolinium salts, we performed nematicidal activity assay using Steinernema feltiae. To determine their impact on microbial proliferation, viability of Escherichia coli and Saccharomyces cerevisiae cells was monitored. For a chemical genetic phenotyping focused on a redox link, 32 redox-related S. cerevisiae mutants were used. DNA double-strand breakage caused by selenazolinium salts was investigated using pulsed-field gel electrophoresis and their physico-chemical properties were assessed using nuclear magnetic resonance (NMR). Results: Some of selenazolinium salts are toxic against S. feltiae at a concentration of 100-500 μM. In E. coli, selenazolium salts display no toxicity at a concentration of 100 μM; however, at a concentration of 500 μM some of them show a statistically relevant toxicity. Similar findings were obtained in wild-type S. cerevisiae cells. Only a few redox-related mutants show higher sensitivity to selenazolinium salts compared to wild-type cells. Selenazolinium salts induce DNA double-strand breaks at moderate doses (10-100 μM).77 Se-NMR shifts reflect some of the trends observed in the biological assays. Conclusion: Our results confirmed that several of selenazolinium salts show a significant biological activity that is executed via an electrophilic attack. © 2017 Bentham Science Publishers.

[No abstract available]

Background: The heterogeneity of Alzheimer disease requires the development of multitarget drugs for treating the symptoms of the disease and its progression. Both cholinergic and monoamine oxidase dysfunctions are involved in the pathological process. Thus, we hypothesized that the development of therapies focused on these targets might be effective. We have developed and assessed a new product, coded ASS234, a multipotent acetyl and butyrylcholinesterase/monoamine oxidase A-B inhibitor with a potent inhibitory effect on amyloid-β aggregation as well as antioxidant and antiapoptotic properties. But there is a need to reliably correlate in vitro and in vivo drug release data. Methods: We examined the effect of ASS234 on cognition in healthy adult C57BL/6J mice in a model of scopolamine- induced cognitive impairment that often accompanies normal and pathological aging. Also, in a characterized transgenic APPswe/PS1ΔE9 mouse model of Alzheimer disease, we examined the effects of short-term ASS234 treatment on plaque deposition and gliosis using immunohistochemistry. Toxicology of ASS234 was assessed using a quantitative high-throughput in vitro cytotoxicity screening assay following the MTT assay method in HepG2 liver cells. Results: In vivo, ASS234 significantly decreased scopolamine-induced learning deficits in C57BL/6J mice. Also, reduction of amyloid plaque burden and gliosis in the cortex and hippocampus was assessed. In vitro, ASS234 exhibited lesser toxicity than donepezil and tacrine. Limitations: The study was conducted in male mice only. Although the Alzheimer disease model does not recapitulate all features of the human disease, it exhibits progressive monoaminergic neurodegeneration. Conclusion: ASS234 is a promising alternative drug of choice to treat the cognitive decline and neurodegeneration underlying Alzheimer disease. © 2017 Joule Inc.

Hypolactasia, or intestinal lactase deficiency, affects more than half of the world population. Currently, xylose quantification in urine after gaxilose oral administration for the noninvasive diagnosis of hypolactasia is performed with the hand-operated nonautomatable phloroglucinol reaction. This work demonstrates that a new enzymatic xylose quantification method, based on the activity of xylose dehydrogenase from Caulobacter crescentus, represents an excellent alternative to the manual phloroglucinol reaction. The new method is automatable and facilitates the use of the gaxilose test for hypolactasia diagnosis in the clinical practice. The analytical validation of the new technique was performed in three different autoanalyzers, using buffer or urine samples spiked with different xylose concentrations. For the comparison between the phloroglucinol and the enzymatic assays, 224 urine samples of patients to whom the gaxilose test had been prescribed were assayed by both methods. A mean bias of -16.08 mg of xylose was observed when comparing the results obtained by both techniques. After adjusting the cut-off of the enzymatic method to 19.18 mg of xylose, the Kappa coefficient was found to be 0.9531, indicating an excellent level of agreement between both analytical procedures. This new assay represents the first automatable enzymatic technique validated for xylose quantification in urine. © 2017 Israel Sánchez-Moreno et al.

The [3 + 2] cycloaddition of two different metal-bound azides, [(Me4cyclam)CoII(N3)]ClO4 and (η5-C5H5)(dppe)RuII(N3), (dppe = Ph2PCH2CH2PPh2) with Cr(0) and W(0) (ethoxy)(alkynyl) Fischer carbenes has been efficiently used for the preparation of polymetallic metal-carbene complexes. The presence of the κ1-bonded metal triazole causes a significant influence on the electronic properties, structure, and reactivity of this new class of Fischer alkoxycarbenes. For the Ru(II) derivatives, their chemical behavior is considerably influenced by the interaction of the (η5-C5H5)(dppe)RuII-triazole moiety with the empty p-carbene orbital that provokes a noticeable decrease in the electrophilicity of the M=C carbon (manifested by the shielding of the 13C NMR chemical shifts). In turn, in the Co(II) derivatives, the incorporation of the (Me4cyclam)CoII moiety diminishes the aromaticity of the triazole ring and has a marked effect on the energy and distribution of the LUSO orbital, mostly resident on the Co(II) fragment. The almost negligible participation of the carbene moiety in the LUSO makes this position unable to react with nucleophiles. The reactions reported in this work constitute the first examples of [3 + 2] cycloaddition of azides and alkynyl Fischer carbene complexes in solution. © 2017 American Chemical Society.

The [2,3]-sigmatropic rearrangement of allylic sulfoxides to allylic sulfenates is a reversible process, generally shifted toward the sulfoxide. In the presence of thiophiles, the sulfenate is trapped, and allylic alcohols are obtained under mild conditions. In most cases, a good transfer of stereochemical information through an ordered transition state is obtained. Furthermore, the ease of coupling this process with other versatile, stereocontrolled reactions has enhanced the usefulness of this protocol. This review aims to provide a comprehensive survey of this rearrangement and its application in the synthesis of natural and bioactive products. © 2017 American Chemical Society.

In this communication we have described the synthesis of 2-amino-6-oxo-1,6-dihydropyridine-3-carbonitrile (4), and the preparation of 5-amino-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridin-2(1H)-one (3 a), a non-hepatotoxic, antioxidant agent, showing moderate, but selective human acetylcholinesterase inhibition. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

A novel series of 5-nitroimidazole-piperazines (4a–j) and 5-nitrothiazole-piperazine (7a–j) have been prepared in good yields. The antigiardial and antitrichomonal activities of these new compounds were evaluated. Majority of the compounds was found to be more active against Giardia lamblia as compared to metronidazole at 24 hours of incubation. After 48 hours of incubation, compounds 4b, 4f, 7c and 7j showed better activity against G. lamblia with IC50 of 15.3, 11.4, 5.9, 13.5 μM respectively compared to metronidazole (17.4 μM). Compounds 4a–j and 7a–j exhibited anti-parasitic activity against T. vaginalis with IC50 ranging from 16.4–88.7 μM and 1.2–86.7 μM at 24 hours and 48 hours of incubation respectively. Compounds 4c and 7e were 15 times more potent than the standard drug, metronidazole. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

New and well-characterized Ag-bis(1,2,3-triazolylidene) complexes having enantiopure (S)-sulfoxides upon sequential treatment with alcohols and Au(I) form separable mixtures of regioisomeric C-unsubstituted Au-1,2,3-triazolylidene complexes. Mechanistic studies and DFT calculations support a desulfinylation process for in situ generated free triazolylidene salts. © 2017 American Chemical Society.

Perfluoroalkyl substances (PFAS) are ubiquitous in the environment, including remote polar regions. To evaluate the role of snow deposition as an input of PFAS to Maritime Antarctica, fresh snow deposition, surface snow, streams from melted snow, coastal seawater, and plankton samples were collected over a three-month period (December 2014-February 2015) at Livingston Island. Local sources of PFASs were significant for perfluoroalkyl sulfonates (PFSAs) and C7-14 perfluoroalkyl carboxylates (PFCAs) in snow but limited to the transited areas of the research station. The concentrations of 14 ionizable PFAS (-PFAS) in freshly deposited snow (760-3600 pg L -1 ) were 1 order of magnitude higher than those in background surface snow (82-430 pg L -1 ). -PFAS ranged from 94 to 420 pg L -1 in seawater and from 3.1 to 16 ng g dw -1 in plankton. Ratios of individual PFAS concentrations in freshly deposited snow relative to surface snow (C SD /C Snow ), snowmelt (C SD /C SM ), and seawater (C SD /C SW ) were close to 1 (from 0.44 to 1.4) for all perfluorooctanesulfonate (PFOS) isomers, suggesting that snowfall does not contribute significantly to PFOS in seawater. Conversely, these ratios for PFCAs ranged from 1 to 33 and were positively correlated with the number of carbons in the PFCA alkylated chain. These trends suggest that snow deposition, scavenging sea-salt aerosol bound PFAS, plays a role as a significant input of PFCAs to the Maritime Antarctica. © 2017 American Chemical Society.

An NMR comparative study of 1,2,3-triazole and triazolium anion recognition units containing sulfoxide, sulfone, and sulfoximine groups at C4 unveils an enhancement in binding ability up to ≈1 kcal/mol in acetone-d6 correlated with a theoretical increase of H5 acidity. DFT calculations provide insight into binding modes in line with experimental data for these receptors. © 2017 American Chemical Society.

O-Ethylation of phthalides with Meerwein's reagent followed by reaction of the ensuing salts with pyrrole, results in the formation of 5-alkoxy-5-phenyl dipyrromethane derivatives, which function as ready precursors of ortho-substituted 8-aryl BODIPY derivatives by reaction with borontrifluoride etherate, an overall process that can be carried out in a one-pot operation. © 2016 American Chemical Society

An unprecedented stereoselective domino reaction of 1,6-enynes with an aryl ring at C3-C4 in the presence of gold(I) catalysts at low temperature is described. This process involves a novel 5-exo-dig cycloisomerization-dimerization sequence to afford formal Diels-Alder adducts that undergo a smooth gold-catalyzed double bond migration at room temperature. In addition, the first examples of the gold mesoionic carbene mediated [2+2+2] cycloaddition of these enynes with benzaldehyde are reported. © 2017 American Chemical Society.

A catalytic, versatile and atom-economical C−H functionalization process that provides a wide variety of cyclic systems featuring methyl-substituted quaternary stereocenters is described. The method relies on the use of a cationic Ir I –bisphosphine catalyst, which promotes a carboxamide-assisted activation of an olefinic C(sp 2 )−H bond followed by exo-cyclization to a tethered 1,1-disubstituted alkene. The extension of the method to aromatic and heteroaromatic C−H bonds, as well as developments on an enantioselective variant, are also described. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

The development of efficient metal-promoted bioorthogonal ligations remains as a major scientific challenge. Demonstrated herein is that azides undergo efficient and regioselective room-temperature annulations with thioalkynes in aqueous milieu when treated with catalytic amounts of a suitable ruthenium complex. The reaction is compatible with different biomolecules, and can be carried out in complex aqueous mixtures such as phosphate buffered saline, cell lysates, fetal bovine serum, and even living bacteria (E. coli). Importantly, the reaction is mutually compatible with the classical CuAAC. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

The therapy of complex neurodegenerative diseases requires the development of multitarget-directed drugs (MTDs). Novel indole derivatives with inhibitory activity towards acetyl/butyrylcholinesterases and monoamine oxidases A/B as well as the histamine H3 receptor (H3R) were obtained by optimization of the neuroprotectant ASS234 by incorporating generally accepted H3R pharmacophore motifs. These small-molecule hits demonstrated balanced activities at the targets, mostly in the nanomolar concentration range. Additional in vitro studies showed antioxidative neuroprotective effects as well as the ability to penetrate the blood–brain barrier. With this promising in vitro profile, contilisant (at 1 mg kg−1 i.p.) also significantly improved lipopolysaccharide-induced cognitive deficits. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

We describe here the synthesis, antioxidant capacity, and biological activities on MAO, ChE, and selected GPCRs, of novel 1-(2,5-dimethoxybenzyl)-4-arylpiperazines 1–10, as well as known N-(2-(2-methyl-5-nitro-1H-imidazol-1-yl))-2-(4-arylpiperazin-1-yl) 11–20 and N-(5-nitrothiazol-2-yl)-2-(4-arylpiperazin-1-yl) 21–29. Some of the new 4-arylpiperazines were found to have low-micromolar affinities for the proteins tested. The most potent MAO inhibitor identified was compound 2-(4-(3-fluorophenyl)-yl)-N-(5-nitrothiazol-2-yl)(27), with an IC50 value of 4.14 ± 0.5 μM, whereas the most potent interaction with a GPCR was 1-(2,5-dimethoxybenzyl)-4-(4-trifluoromethylphenyl) (5) for the 5-HT6 serotonin receptor, with a Ki value of 0.7 μM. Interestingly, some of the compounds described here showed impressive antioxidant potential. Of mention, compounds 1, 6, 7, and 23 had trolox/equivalent ORAC values of 9.10, 8.80, 8.82, and 9.42, respectively, all of them being significantly higher than the TE determined for ferulic acid (3.74), a standard antioxidant. Among all molecules synthesized and tested, compound 23 can be regarded as an interesting low-micromolar MAO−B/5-HT6 dual inhibitor lead with potent antioxidant properties. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Hexacarbonyldicobalt–C-3-alkynyl-substituted glycal derivatives, when treated with BF3·OEt2 give rise to Nicholas-stabilized Ferrier cation intermediates (Ferrier–Nicholas cations) that react with alcohols or C-nucleophiles to give C-3-branched 2,3-unsaturated glycosides or C-glycosides, respectively. α-C-Glycosides were the sole compounds obtained when allyltrimethylsilane was used as the nucleophile. On the contrary, the reaction of C-3-alkynylglycals with heteroaryl or alcohol nucleophiles led to anomeric mixtures in which the β-anomers prevailed. The presence of the hexacarbonyldicobalt–C-3-alkynyl substituent seems to be of key importance in the stereoselectivity of these transformations, since the reaction of C-3-alkynylglycals – devoid of the hexacarbonyldicobalt moiety – showed a preferred α-stereoselectivity. Furthermore, a bis(indolyl) linear compound was obtained from the reaction of a hexacarbonyldicobalt–C-3-alkynylglycal with 2 equiv. of indole. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

There is a need to develop additional effective therapies for ischemic stroke. Nitrones, which were first developed as reactive oxygen species (ROS)-trapping compounds, have been proposed as neuroprotective agents for ischemic stroke, a ROS-related disorder. The previous reported ROS-trapping compound, quinolyl nitrone RP19, is here being assayed to induce neuroprotection to ischemia-reperfusion injury in three experimental ischemia models: (i) oxygen-glucose deprivation (OGD) on primary neuronal cultures; (ii) transient global cerebral ischemia in four-vessel occlusion model; and (iii) transient focal cerebral ischemia in middle cerebral artery occlusion (tMCAO) model. RP19 (50 μM) induced long-term neuroprotection at 5 days of recovery after OGD in primary neuronal cultures, evaluated by cell viability assay, and decreased both ROS formation and lipid peroxidation upon recovery after OGD. Furthermore, treatment of animals with RP19 at the onset of reperfusion after either global or focal ischemia, at the dose range that was demonstrated to be neuroprotective in neuronal cultures, decreased neuronal death and apoptosis induction, reduced the size of infarct, and improved the neurological deficit scores after 48 h or 5 days of reperfusion after ischemia. The molecule proposed, quinolyl nitrone RP19, induced substantial neuroprotection on experimental ischemia in neuronal cells, and against ischemic injury following transient brain ischemia in treated animals. This molecule may have potential therapeutic interest in ischemic stroke and to reduce the reoxygenation-induced injury after induced reperfusion. © 2017 American Chemical Society.