Photodegradable Antimicrobial Agents: Synthesis and Mechanism of Degradation

As a strategy to inactivate antimicrobial agents after use, we designed a range of ethanolamine derivatives where four of them possessed interesting activity. The ethanolamine moiety facilitates photodecomposition, which in a potential drug will take place after use. Herein, the synthetic preparation of these compounds and the mechanism of photoinactivation are described.publishedVersio

Evaluation of photodegradable chitin synthetase inhibitors for the treatment of salmon lice (Lepeophtheirus salmonis)

Some photolabile ethanolamine analogues of the chitin synthetase inhibitors diflubenzuron, teflubenzuron, and lufenuron were tested for activity as anti-lice compounds towards salmon lice (Lepeophtheirus salmonis). Two teflubenzuron analogues (2 and 3) exhibited interesting biological activity whereas their corresponding photodecomposition products were inactive. One of the analogues (3) decomposes completely when irradiated at pH 8, a relevant pH for seawater. In comparison, diflubenzuron showed a 66% photodecomposition under identical conditions. Thus, ethanolamine 3 is an interesting lead compound in the search for a powerful, environmentally friendly chemical to use in salmon-lice treatment.publishedVersio

Natural peptides with antioxidant activity from Atlantic cod and Atlantic salmon residual material

Summary. Water-soluble peptides/proteins with molecular weight below 10 kDa were isolated from residual material of cod (liver, skin, and cod mix i.e. skin, frames, and viscera), and salmon (skin, and salmon mix i.e. skin, frames, and viscera) by cut-off filtration. Peptide motifs with reported bioactivity were identified in all samples by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) (Orbitrap), bioinformatics, and database search. Peptides with potential type 2 diabetes, cardio system, immunomodulation, prolyl endopeptidase (PEP), and antioxidant activity were detected. The potential antioxidant activity in the samples was confirmed by two antioxidant assays, namely hydroxyl radical scavenging activity (HRSA), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical cation decolorization assay. In these assays the salmon samples were found to possess higher antioxidant activity than the cod samples. All samples except the cod skin were found to have higher antioxidant activity than alanine-histidine (AH), a dipeptide with known antioxidant activity. Industrial relevance. Residual material from fisheries and aquaculture makes up large quantities of material. Although previously regarded as waste this material has valuable components that are of interest for the biotech industry. The fractionation process utilized in this work offers the possibility for simple isolation of interesting peptides with antioxidant activity. This method should be of interest for the food industry and biotech industry for product development

Regiodivergent Synthesis of 11H-Indolo[3,2-c]quinolines and Neocryptolepine from a Common Starting Material

A large number of diversely functionalized analogs of the bioactive natural products neocryptolepine and isocryptolepine have been prepared from a series of 3-bromoquinoline derivatives. The neocryptolepines were obtained by a Pd0-catalyzed C−C bond coupling followed by C−N bond formation in yields up to 80 %, whereas the indoloquinolines were prepared by a Suzuki-Miyaura cross-coupling followed by azidation-photochemical cyclization in yields ranging from traces to 95 % yield

Total synthesis of tubastrine and 3-dehydroxy tubastrine by microwave-assisted cross-coupling reactions

The first syntheses of tubastrine and 3-dehydroxy tubastrine are described. The target compounds were prepared in four consecutive steps from commercially available starting materials. The central scaffold was formed by a microwave-assisted C–N cross-coupling reaction between 1,3-bis(tert-butoxycarbonyl)-guanidine and (E)-((4-(2-iodovinyl)-1,2-phenylene)bis(oxy))bis(tert-butyldimethylsilane) and (E)-tert-butyl(4-(2-iodovinyl)phenoxy)–dimethylsilane, respectively. The aryl vinyl iodides were obtained by a Hunsdiecker–Borodin-type reaction of aryl acrylic acids, which were easily available from trans-caffeic acid or trans-p-coumaric acid.acceptedVersio

Substituted Two- To Five-Ring Polycyclic Aromatic Compounds Are Potent Agonists of Atlantic Cod (Gadus morhua) Aryl Hydrocarbon Receptors Ahr1a and Ahr2a

Polycyclic aromatic hydrocarbons (PAHs) are among the most toxic and bioavailable components found in petroleum and represent a high risk to aquatic organisms. The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other planar aromatic hydrocarbons, including certain PAHs. Ahr acts as a xenosensor and modulates the transcription of biotransformation genes in vertebrates, such as cytochrome P450 1A (cyp1a). Atlantic cod (Gadus morhua) possesses two Ahr proteins, Ahr1a and Ahr2a, which diverge in their primary structure, tissue-specific expression, ligand affinities, and transactivation profiles. Here, a luciferase reporter gene assay was used to assess the sensitivity of the Atlantic cod Ahrs to 31 polycyclic aromatic compounds (PACs), including two- to five-ring native PAHs, a sulfur-containing heterocyclic PAC, as well as several methylated, methoxylated, and hydroxylated congeners. Notably, most parent compounds, including naphthalene, phenanthrene, and partly, chrysene, did not act as agonists for the Ahrs, while hydroxylated and/or alkylated versions of these PAHs were potent agonists. Importantly, the greater potencies of substituted PAH derivatives and their ubiquitous occurrence in nature emphasize that more knowledge on the toxicity of these environmentally and toxicologically relevant compounds is imperative.publishedVersio

Study of the long-finned pilot whale (Globicephala melas) bile content - An indicator of ocean health

Globicephala melas has been harvested in the Faroe Islands for centuries. Given the distances travelled by this species, tissue/body fluid samples represent unique matrices to be considered as an integration of environmental condition and pollution status of their prey. For the first time, bile samples were analysed for presence of polycyclic aromatic hydrocarbon (PAH) metabolites and protein content. Concentrations of 2- and 3-ring PAH metabolites ranged from 11 to 25 μg mL−1 pyrene fluorescence equivalents. In total, 658 proteins were identified and 61,5 % were common amongst all individuals. Identified proteins were integrated into in silico software and determined that the top predicted disease and functions were neurological diseases, inflammation, and immunological disorders. The metabolism of reactive oxygen species (ROS) was predicted to be dysregulated, which can have consequences to both the protection against ROS produced during dives and contaminant exposures. The obtained data is valuable for understanding metabolism and physiology of G. melas.publishedVersio

Bioaccumulation potential of the tricyclic antidepressant amitriptyline in a marine Polychaete, Nereis virens

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A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE)

The synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition was employed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The heterodimers were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The heterodimers displayed preferential inhibition (> 9) of BuChE over AChE in the micromolar concentration range (IC50 = 7–50 µM). For the most potent inhibitor of BuChE, Cornish-Bowden plots were used, which demonstrated that it behaves as a mixed inhibitor. Modelling studies of the same inhibitor demonstrated that the benzotriazole and 1-deoxynojirimycin moiety is accommodated in the peripheral anionic site and catalytic anionic site, respectively, of AChE. The binding mode to BuChE was different as the benzotriazole moiety is accommodated in the catalytic anionic site.publishedVersio

The use of Palladium on Magnetic Support as Catalyst for Suzuki-Miyaura Cross-Coupling Reactions

The development of new solid supports for palladium has received a lot of interest lately. These catalysts have been tested in a range of cross-coupling reactions, such as Suzuki–Miyaura, Mizoroki-Heck, and Sonogashira cross-coupling reactions, with good outcomes. Attaching the catalyst to a solid support simplifies the operations required in order to isolate and recycle the catalyst after a reaction has completed. Palladium on solid supports made of magnetic materials is particularly interesting since such catalysts can be removed very simply by utilizing an external magnet, which withholds the catalyst in the reaction vessel. This review will showcase some of the latest magnetic solid supports for palladium and highlight these catalysts’ performance in Suzuki–Miyaura cross-coupling reactions