Selenium-containing compounds: a new hope for innovative treatments in Alzheimer's disease and Parkinson's disease.

Neurodegenerative diseases are challenging to cure. To date, no cure has been found for Alzheimer's disease or Parkinson's disease, and current treatments are able only to slow the progression of the diseases and manage their symptoms. After an introduction to the complex biology of these diseases, we discuss the beneficial effect of selenium-containing agents, which show neuroprotective effects in vitro or in vivo. Indeed, selenium is an essential trace element that is being incorporated into innovative organoselenium compounds, which can improve outcomes in rodent or even primate models with neurological deficits. Herein, we critically discuss recent findings in the field of selenium-based applications in neurological disorders.

The future in the litter bin - bioconversion of food waste as driver of a circular bioeconomy.

Bioconversion of organic waste requires the development and application of rather simple, yet robust technologies capable of transferring biomass into energy and sustainable materials for the future. Food waste plays a significant role in this process as its valorisation reduces waste and at the same time avoids additional exploitation of primary resources. Nonetheless, to literally become "litterate". extensive research into such robust large-scale methods is required. Here, we highlight some promising avenues and materials which fulfill these "waste to value" requirements, from various types of food waste as sustainable sources for biogas, bioethanol and biodiesel to fertilizers and antioxidants from grape pomace, from old-fashioned fermentation to the magic of anaerobic digestion.

Chalcogen-Varied Imidazolone Derivatives as Antibiotic Resistance Breakers in Staphylococcus aureus Strains.

In this study, a search for new therapeutic agents that may improve the antibacterial activity of conventional antibiotics and help to successfully overcome methicillin-resistant Staphylococcus aureus (MRSA) infections has been conducted. The purpose of this work was to extend the scope of our preliminary studies and to evaluate the adjuvant potency of new derivatives in a set of S. aureus clinical isolates. The study confirmed the high efficacy of piperazine derivatives of 5-arylideneimidazol-4-one (7-9) tested previously, and it enabled the authors to identify even more efficient modulators of bacterial resistance among new analogs. The greatest capacity to enhance oxacillin activity was determined for 1-benzhydrylpiperazine 5-spirofluorenehydantoin derivative (13) which, at concentrations as low as 0.0625 mM, restores the effectiveness of ß-lactam antibiotics against MRSA strains. In silico studies showed that the probable mechanism of action of 13 is related to the binding of the molecule with the allosteric site of PBP2a. Interestingly, thiazole derivatives tested were shown to act as both oxacillin and erythromycin conjugators in S. aureus isolates, suggesting a complex mode of action (i.e., influence on the Msr(A) efflux pump). This high enhancer activity indicates the high potential of imidazolones to become commercially available antibiotic adjuvants.

Selenoneine-inspired selenohydantoins with glutathione peroxidase-like activity.

Chronic diseases such as cystic fibrosis, inflammatory bowel diseases, rheumatoid arthritis, and cardiovascular illness have been linked to a decrease in selenium levels and an increase in oxidative stress. Selenium is an essential trace element that exhibits antioxidant properties, with selenocysteine enzymes like glutathione peroxidase being particularly effective at reducing peroxides. In this study, a series of synthetic organoselenium compounds were synthesized and evaluated for their potential antioxidant activities. The new selenohydantoin molecules were inspired by selenoneine and synthesized using straightforward methods. Their antioxidant potential was evaluated and proven using classical radical scavenging and metal-reducing methods. The selenohydantoin derivatives exhibited glutathione peroxidase-like activity, reducing hydroperoxides. Theoretical calculations using Density Functional Theory (DFT) revealed the selenone isomer to be the only one occurring in solution, with selenolate as a possible tautomeric form in the presence of a basic species. Cytocompatibility assays indicated that the selenohydantoin derivatives were non-toxic to primary human aortic smooth muscle cells, paving the way for further biological evaluations of their antioxidant activity. The results suggest that selenohydantoin derivatives with trifluoro-methyl (-CF3) and chlorine (-Cl) substituents have significant activities and could be potential candidates for further biological trials. These compounds may contribute to the development of effective therapies for chronic diseases such cardiovascular diseases.

Bioorganic Chemistry: Current and Future Perspectives.

Bioorganic Chemistry is an emerging field developing at the interface between the traditional fields of Chemistry and Biochemistry [...].

The redox riddle of selenium sulfide.

Selenium sulfide, in analogy with selenium dioxide, is often considered as SeS2. At closer inspection, however, selenium sulfide represents a large family of rather complicated molecules which differ depending on the mode of preparation. Together, these compounds share extraordinarily low solubility in virtually any solvent with a biological activity rather impressive for such simple molecules. The surface reactivity of such microscopic and nanoscopic materials, prepared chemically or by fermentation, may provide an answer to this riddle and explain activities by a combination of physical, redox, metal binding, covalent, and non-covalent interactions with biomolecules and cells.

Synthesis and bioassay of 3-Aryl -1-(pyridin-4-yl)benzo[4,5]imidazo[1,2-d][1,2,4]- triazin-4(3H)-ones as anti-cancer agents.

Four novel 3-Aryl -1-(pyridin-4-yl)benzo[4,5]imidazo[1,2-d][1,2,4]- triazin-4(3H)-ones derivatives (C1 to C4) have been designed, synthesized, and evaluated for their anticancer activity. The structure of compounds was characterized by IR,1H NMR, 13C NMR and high-resolution mass (HRMS). The crystal structures of C1, C2 and C4 were previously determined by single-crystal X-ray analysis.The results from docking experiments with EGFR suggested the binding of the compounds at the active site of EGFR. The new compounds exhibited different levels of cytotoxicity against HCC1937 and MCF7 breast cancer cells. Results of the MTT assay identified C3 as the most cytotoxic of the series against both MCF7 and HCC1937 breast cancer cell lines with IC50 values of 36.4 and 48.2 µM, respectively. In addition to its ability to inhibit cell growth and colony formation ability, C3 also inhibited breast cancer cell migration. Western blotting results showed that C3 treatment inhibited EGFR signaling and induced cell cycle arrest and apoptosis as indicated by the low level of p-EGFR and p-AKT and the increasing levels of p53, p21 and cleaved PARP. Our work represents a promising starting point for the development of a new series of compounds targeting cancer cells.

It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities.

In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (ortho-quinone/para-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of para-naphthoquinones and subsequent conjugation with different ortho-quinoidal moieties. As anticipated, our study identified several compounds with IC50 values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized para-quinones coupled with ortho-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango!

To Cut the Mustard: Antimicrobial Activity of Selenocyanates on the Plate and in the Gas Phase.

Organic selenocyanates (RSeCN) are among the most reactive and biologically active Se species, often exhibiting a pronounced cytotoxic activity against mammalian cells and microorganisms. Various aromatic selenocyanates have been synthesized and, similar to some of the most Reactive Sulfur Species (RSS), such as allicin, found to be active against a range of bacteria, including Escherichia coli, Pseudomonas syringae and Micrococcus luteus, and fungi, including Verticillium dahlia, Verticillium longisporum, Alternaria brassicicola, and Botrytis cinerea, even via the gas phase. The highest antimicrobial activity has been observed for benzyl selenocyanate, which inhibited the growth of all bacteria considerably, even at the lowest tested concentration of 50 µM. Notably, neither the analogues thiocyanate (BTC) nor isothiocyanate (BITC) show any of these activities, rendering this selenium motif rather special in activity and mode of action. Eventually, these findings advocate a range of potential applications of organic selenocyanates in medicine and agriculture.

Daniellia oliveri (Rolfe) Hutch and Dalziel: Antimicrobial Activities, Cytotoxicity Evaluation, and Phytochemical Identification by GC-MS.

During a previous study that identified plants used in traditional medicine in Togo to treat infectious diseases, Daniellia oliveri was specifically reported to treat intertrigo and candidiasis. Consequently, to explore the anti-infective potential of this plant, we investigated the antibacterial and the antifungal activity of the plant's parts, as well as the cytotoxic activities of raw extracts and subsequent fractions, and the chemical composition of the most active fractions. In order to evaluate the antimicrobial activity, MICs were determined using the broth dilution method. Then, the most active fractions were evaluated for cytotoxicity by using normal human cells (MRC-5 cells) via the MTT assay. Finally, the most active and not toxic fractions were phytochemically investigated by GC-MS. Interestingly, all the raw extracts and fractions were active against the bacteria tested, with MICs ranging from 16 µg/mL to 256 µg/mL, while no antifungal activity was observed at 256 µg/mL, the highest tested concentration. Moreover, no toxicity was observed with most of the active fractions. The subsequent chemical investigation of the most interesting fractions led to identifying terpenes, phytosterols, phenolic compounds, and fatty acids as the main compounds. In conclusion, this study demonstrated that D. oliveri possesses valuable antibacterial activities in accordance with traditional use.

Ribes nigrum L. Extract-Mediated Green Synthesis and Antibacterial Action Mechanisms of Silver Nanoparticles.

Silver nanoparticles (Ag NPs) represent one of the most widely employed metal-based engineered nanomaterials with a broad range of applications in different areas of science. Plant extracts (PEs) serve as green reducing and coating agents and can be exploited for the generation of Ag NPs. In this study, the phytochemical composition of ethanolic extract of black currant (Ribes nigrum) leaves was determined. The main components of extract include quercetin rutinoside, quercetin hexoside, quercetin glucuronide, quercetin malonylglucoside and quercitrin. The extract was subsequently employed for the green synthesis of Ag NPs. Consequently, R. nigrum leaf extract and Ag NPs were evaluated for potential antibacterial activities against Gram-negative bacteria (Escherichia coli ATCC 25922 and kanamycin-resistant E. coli pARG-25 strains). Intriguingly, the plant extract did not show any antibacterial effect, whilst Ag NPs demonstrated significant activity against tested bacteria. Biogenic Ag NPs affect the ATPase activity and energy-dependent H+-fluxes in both strains of E. coli, even in the presence of N,N'-dicyclohexylcarbodiimide (DCCD). Thus, the antibacterial activity of the investigated Ag NPs can be explained by their impact on the membrane-associated properties of bacteria.

Seleno-vs. thioether triazine derivatives in search for new anticancer agents overcoming multidrug resistance in lymphoma.

Lymphomas are still difficult to treat even with modern therapies as, among others, multidrug resistance (MDR) is often counteracting a successful cancer therapy. P-gp/ABC-transporters are well-known for their crucial role in the main tumour MDR mechanism, eliminating drugs and cytotoxic substances from the cancer cell by efflux, and their modulators are promising for innovative therapy, but none has been approved in the pharmaceutical market yet. Herein, we have designed, synthesised and analysed 30 novel seleno- and thioether 1,3,5-triazine derivatives conducting comprehensive studies to evaluate their potential application in human JURKAT lymphoma cells. Among the new compounds, four (11, 12, 13 and 23) were much more effective than the reference inhibitor verapamil, being potent ABCB1 inhibitors already at 2 µM, while 5 and 15 showed very potent ABCB1 inhibitory activity only at 20 µM. Results of P-gp ATPase assays, supported with docking studies, indicated the competitive substrate mode of modulating action for 15, while ABCB1, ABCC1 and ABCG2 genes expression induction by 15 with q-PCR was confirmed. All compounds were evaluated for their cytotoxic and antiproliferative properties in both sensitive (PAR) and resistant (MDR) mouse T-lymphoma cell lines, and compound 15, also considering its promising ABCB1 inhibition properties, was revealed to be the best compound in terms of its cytotoxic effect (IC50: 16.73 µM) as well as concerning the antiproliferative effect (IC50: 5.35 µM) in MDR cells. Regarding the mechanistic studies looking at the cell cycle, the thioether 15 and selenium derivatives 26 and 29 were significantly effective in the regulation of cell cycle-related genes alone or in co-treatment with doxorubicin counteracting Cyclin D1 and E1 expression and increasing p53 and p21 levels, shedding first light on their mechanism of action. In summary, we explored the chemical space of seleno- and thioether 1,3,5-triazine derivatives with interesting activity against lymphoma. Especially compound 15 is worthy of being studied deeper to evaluate its precise mode of action further as well it can be improved regarding its potency and drug-likeness.

A Whiff of Sulfur: One Wind a Day Keeps the Doctor Away.

Reactive Sulfur Species (RSS), such as allicin from garlic or sulforaphane from broccoli, are fre-quently associated with biological activities and possible health benefits in animals and humans. Among these Organic Sulfur Compounds (OSCs) found in many plants and fungi, the Volatile Sulfur Compounds (VSCs) feature prominently, not only because of their often-pungent smell, but also because they are able to access places which solids and solutions cannot reach that easily. Indeed, inorganic RSS such as hydrogen sulfide (H2S) and sulfur dioxide (SO2) can be used to lit-erally fumigate entire rooms and areas. Similarly, metabolites of garlic, such as allyl methyl sulfide (AMS), are formed metabolically in humans in lower concentrations and reach the airways from inside the body as part of one's breath. Curiously, H2S is also formed in the gastrointestinal tract by gut bacteria, and the question of if and for which purpose this gas then crosses the barriers and enters the body is indeed a delicate matter for equally delicate studies. In any case, nature is surprisingly rich in such VSCs, as fruits (for instance, the infamous durian) demonstrate, and therefore these VSCs represent a promising group of compounds for further studies.

Selenium and tellurium in the development of novel small molecules and nanoparticles as cancer multidrug resistance reversal agents.

Selenium is an essential trace element that is crucial for cellular antioxidant defense against reactive oxygen species (ROS). Recently, many selenium-containing compounds have exhibited a wide spectrum of biological activities that make them promising scaffolds in Medicinal Chemistry, and, in particular, in the search for novel compounds with anticancer activity. Similarly, certain tellurium-containing compounds have also exhibited substantial biological activities. Here we provide an overview of the biological activities of seleno- and tellurocompounds including chemopreventive activity, antioxidant or pro-oxidant activity, modulation of the inflammatory processes, induction of apoptosis, modulation of autophagy, inhibition of multidrug efflux pumps such as P-gp, inhibition of cancer metastasis, selective targeting of tumors and enhancement of the cytotoxic activity of chemotherapeutic drugs, as well as overcoming tumor drug resistance. A review of the chemistry of the most relevant seleno- or tellurocompounds with activity against resistant cancers is also presented, paying attention to the synthesis of these compounds and to the preparation of bioactive selenium or tellurium nanoparticles. Based on these data, the use of these seleno- and tellurocompounds is a promising approach in the development of strategies that can drive forward the search for novel therapies or adjuvants of current therapies against drug-resistant cancers.

Potential health effects of brewers' spent grain as a functional food ingredient assessed by markers of oxidative stress and inflammation following gastro-intestinal digestion and in a cell model of the small intestine.

Brewer's spent grains (BSG) are a by-product of the beer-brewing industry, often employed as animal feeding stuffs. With BSG being rich not only in proteins, lipids, and dietary fiber but also in certain phytochemicals, it constitutes a potentially valuable food source that could be employed as a functional food, e.g. against chronic inflammatory diseases. Several types of bread were prepared with various amounts of BSG as flour replacement (0, 10, 20, 40, 60, 80 and 100%), either employing wet BSG or dried BSG after pressing. Total phenolics, flavonoids, insoluble dietary fiber, as well as antioxidant capacity (FRAP, ABTS) were measured in the bread, before and after simulated gastro-intestinal digestion. Furthermore, we investigated digested BSG and bread-containing BSG for their capability to alter oxidative stress (Nrf2, malondialdehyde) and inflammation (IL-6, IL-8, NO, and PGE2) in a Caco-2 cell culture model of the small intestine. Incorporation of BSG significantly and dose-dependently enhanced the amount of dietary fiber in the product, as well as total phenolics, flavonoids, and antioxidant capacity, by over 10-fold, 3-fold, 4-fold and 5-fold, respectively, when replacing all of the flour with BSG. This pattern remained after in vitro digestion. However, digesta failed to show significant antioxidant or anti-inflammatory effects on the biomarkers observed in the cell model. Consuming 150 g of such a BSG-bread (wet based) would supply the proposed RDA of 25 g d-1 dietary fiber and could be a healthy product valorizing BSG.

Bert Vallee-A 20th Century Adventure(r) in Zincology.

Prelude [...].

Knowledge into the Practice against COVID-19: A Cross-Sectional Study from Ghana.

The COVID-19 pandemic has affected populations globally, including Ghana. Knowledge of the COVID-19 disease, and the application of preventive public health interventions are pivotal to its control. Besides a lockdown, measures taken against the spread of the virus include the wearing of face masks, social distancing, regular hand washing with soap and, more recently, vaccination against the virus. In order to establish a possible link between the knowledge of the disease and compliance with preventive measures, including vaccination, a cross-sectional study employing an interview-structured questionnaire was conducted in six regions of Ghana (n = 1560). An adequate level of knowledge of COVID-19 (69.9%) was reported. The linear multiple regression analysis further explicated the differences in the knowledge of COVID-19 among the respondents by their knowledge of cholera and influenza (adjusted R-Square = 0.643). Despite this profound knowledge of the illness, two thirds of the respondents were unwilling to follow basic preventive measures and only 35.3% were willing to be vaccinated. Amazingly, neither knowledge of COVID-19 nor the socio-demographic characteristics had any meaningful influence on the practice of preventive measures. Personal attitude leading to efficient public compliance with preventive measures, therefore, is a critical issue demanding special attention and effective interventions by the government and locals with authority to curb the spread of the pandemic which surpasses the traditional channels of public health communication. This includes a roll-out of persuasion, possibly including public figures and influencers, and in any case, a balanced and open discussion addressing the acceptance of the COVID-19 vaccine in order to avoid new variants and comparable problems currently facing many countries of Western Europe. Indeed, a profound hesitancy against vaccination may turn African countries such as Ghana for many years into hotspots of new viral variants.

It takes two to tango: synthesis of cytotoxic quinones containing two redox active centers with potential antitumor activity.

We report the synthesis of 47 new quinone-based derivatives via click chemistry and their subsequent evaluation against cancer cell lines and the control L929 murine fibroblast cell line. These compounds combine two redox centers, such as an ortho-quinone/para-quinone or quinones/selenium with the 1,2,3-triazole nucleus. Several of these compounds present IC50 values below 0.5 µM in cancer cell lines with significantly lower cytotoxicity in the control cell line L929 and good selectivity index. Hence, our study confirms the use of a complete and very diverse range of quinone compounds with potential application against certain cancer cell lines.

EPR Study of KO2 as a Source of Superoxide and •BMPO-OH/OOH Radical That Cleaves Plasmid DNA and Detects Radical Interaction with H2S and Se-Derivatives.

Superoxide radical anion (O2•-) and its derivatives regulate numerous physiological and pathological processes, which are extensively studied. The aim of our work was to utilize KO2 as a source of O2•- and the electron paramagnetic resonance (EPR) spin trapping 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO) technique for the preparation of •BMPO-OOH and/or •BMPO-OH radicals in water solution without DMSO. The method distinguishes the interactions of various compounds with •BMPO-OOH and/or •BMPO-OH radicals over time. Here, we show that the addition of a buffered BMPO-HCl mixture to powdered KO2 formed relatively stable •BMPO-OOH and •BMPO-OH radicals and H2O2, where the •BMPO-OOH/OH ratio depended on the pH. At a final pH of ~6.5-8.0, the concentration of •BMPO-OOH radicals was ≥20 times higher than that of •BMPO-OH, whereas at pH 9.0-10.0, the •BMPO-OH radicals prevailed. The •BMPO-OOH/OH radicals effectively cleaved the plasmid DNA. H2S decreased the concentration of •BMPO-OOH/OH radicals, whereas the selenium derivatives 1-methyl-4-(3-(phenylselanyl) propyl) piperazine and 1-methyl-4-(4-(phenylselanyl) butyl) piperazine increased the proportion of •BMPO-OH over the •BMPO-OOH radicals. In conclusion, the presented approach of using KO2 as a source of O2•-/H2O2 and EPR spin trap BMPO for the preparation of •BMPO-OOH/OH radicals in a physiological solution could be useful to study the biological effects of radicals and their interactions with compounds.