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.

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.

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.

Molecular Insights into an Antibiotic Enhancer Action of New Morpholine-Containing 5-Arylideneimidazolones in the Fight against MDR Bacteria.

In the search for an effective strategy to overcome antimicrobial resistance, a series of new morpholine-containing 5-arylideneimidazolones differing within either the amine moiety or at position five of imidazolones was explored as potential antibiotic adjuvants against Gram-positive and Gram-negative bacteria. Compounds (7-23) were tested for oxacillin adjuvant properties in the Methicillin-susceptible S. aureus (MSSA) strain ATCC 25923 and Methicillin-resistant S. aureus MRSA 19449. Compounds 14-16 were tested additionally in combination with various antibiotics. Molecular modelling was performed to assess potential mechanism of action. Microdilution and real-time efflux (RTE) assays were carried out in strains of K. aerogenes to determine the potential of compounds 7-23 to block the multidrug efflux pump AcrAB-TolC. Drug-like properties were determined experimentally. Two compounds (10, 15) containing non-condensed aromatic rings, significantly reduced oxacillin MICs in MRSA 19449, while 15 additionally enhanced the effectiveness of ampicillin. Results of molecular modelling confirmed the interaction with the allosteric site of PBP2a as a probable MDR-reversing mechanism. In RTE, the compounds inhibited AcrAB-TolC even to 90% (19). The 4-phenylbenzylidene derivative (15) demonstrated significant MDR-reversal "dual action" for ß-lactam antibiotics in MRSA and inhibited AcrAB-TolC in K. aerogenes. 15 displayed also satisfied solubility and safety towards CYP3A4 in vitro.

PlantCrystals-Nanosized Plant Material for Improved Bioefficacy of Medical Plants.

PlantCrystals are obtained by milling plant material to sizes <10 µm. Due to the disruption of the plant cells, active compounds are easily released, rendering the PlantCrystal technology an effective and low-cost process for the production of environmentally friendly plant extracts. The extracts can be used to produce phytomedicines, nutritional supplements or cosmetic products. Previous studies could already demonstrate the use of PlantCrystals to improve the antimicrobial or antifungal activity of different plants. This study investigated whether PlantCrystal technology is suitable to produce plant derived formulations with high antioxidant capacity. The study also aimed to identify the most suitable production methods for this. METHODS: Various plant materials and parts of plants, i.e., seeds, leaves and flowers, and different methods were employed for the production. PlantCrystals were characterized regarding size, physical stability and antioxidant capacity (AOC). RESULTS: PlantCrystals with particles <1 µm were produced from the different plant materials. Both production methods, i.e., high-pressure homogenization, bead milling or the combination of both were suitable to obtain PlantCrystals. Nano milling of the plant material greatly affected their AOC and resulted in formulations with distinctly higher AOC when compared to classical extracts. CONCLUSIONS: Rendering plant material into small sized particles is highly effective to obtain plant extracts with high biological efficacy.

Origanum vulgare L. extract-mediated synthesis of silver nanoparticles, their characterization and antibacterial activities.

Plant extracts serve as reducing and coating agents and are, therefore, commonly employed for the generation of silver (Ag) nanoparticles (NPs). Plant extract mediated synthesis of Ag NPs is a green, environmentally friendly and cost-effective technique which offers a new and potential alternative to chemically synthesized NPs, decreasing the utilization of hazardous and toxic chemicals and protecting the environment. Origanum vulgare L. extracts were evaluated for total flavonoid and phenol content. The free radical scavenging activity was determined employing 2,2-diphenyl-1-picrylhydrazyl assay. Ag NPs were produced exploiting ethanolic extracts of O. vulgare L. leaves. The generation of Ag NPs was carried out both in light and dark conditions. The biosynthesized Ag NPs were characterized employing microscopic and spectroscopic techniques. Antibacterial activities of Ag NPs were determined following appropriate methods. The results revealed that energy of photons was required to reduce Ag+ to Ag0. According to scanning electron microscopy reports, biologically formed Ag NPs ranged in size from 1 to 50 nmand were presented instability causing aggregation. They indicated that O. vulgare L. extracts were rich in flavonoids and phenols and exhibited strong antioxidant activity. Ag NPs exhibited good antibacterial activity immediately after production. Gram-positive strains showed higher sensitivity to Ag NPs compared to Gram-negative stains. Ag NPs can serve as an effective antibacterial agent against antibiotic-resistant strains. The kanamycin-resistant strain was more sensitive to Ag NPs than the ampicillin-resistant strain. Thus, Origanum extract-mediated synthesized Ag NPs can be recommended as alternative effective antibacterial agents, but their activity depended on bacterial species and strains.

Biological Activity of Hydrophilic Extract of Chlorella vulgaris Grown on Post-Fermentation Leachate from a Biogas Plant Supplied with Stillage and Maize Silage.

Algae are employed commonly in cosmetics, food and pharmaceuticals, as well as in feed production and biorefinery processes. In this study, post-fermentation leachate from a biogas plant which exploits stillage and maize silage was utilized as a culture medium for Chlorella vulgaris. The content of polyphenols in hydrophilic extracts of the Chlorella vulgaris biomass was determined, and the extracts were evaluated for their antioxidant activity (DPPH assay), antibacterial activity (against Escherichia coli, Lactobacillus plantarum, Staphylococcus aureus, Staphylococcus epidermidis) and antifungal activity (against Aspergillus niger, Candida albicans, Saccharomyces cerevisiae). The use of the post-fermentation leachate was not found to affect the biological activity of the microalgae. The aqueous extract of Chlorella vulgaris biomass was also observed to exhibit activity against nematodes. The results of this study suggest that Chlorella vulgaris biomass cultured on post-fermentation leachate from a biogas plant can be successfully employed as a source of natural antioxidants, food supplements, feed, natural antibacterial and antifungal compounds, as well as in natural methods of plant protection.

The Caucasian flora: a still-to-be-discovered rich source of antioxidants.

Cellular redox homeostasis is a state of balance between the formation of Usually Reactive Oxygen and / or Nitrogen Species (ROS/RNS), endogenous antioxidant defence systems, and exogenous dietary antioxidants. The disturbance of redox homeostasis, by the overproduction of endogenous ROS/RNS, may increase the risk of development of so-called civilisation diseases. The solution seems to be either the increased production of endogenous or consumption of exogenous antioxidants. Plant-borne antioxidants act via different chemical and molecular mechanisms, such as decreasing the level of oxidative damage in cells directly by reacting with ROS/RNS or indirectly - by inhibition of the activity and expression of free radical generating enzymes or by enhancing the activity or expression of intracellular antioxidant defence enzymes. Despite the fact that the Caucasian flora is rich of health promoting edible/medicinal plants, recent studies concerning the biological activity of these plants are very scarce. This review is summarising the state-of-art on the health-promoting potential of plants representing the Caucasian flora, whose antioxidant capacity have been investigated in various in vitro models.

Selenium Donors at the Junction of Inflammatory Diseases.

Selenium is an essential non-metal trace element, and the imbalance in the bioavailability of selenium is associated with many diseases ranking from acute respiratory distress syndrome, myocardial infarction and renal failure (Se overloading) to diseases associated with chronic inflammation like inflammatory bowel diseases, rheumatoid arthritis, and atherosclerosis (Se unload). The only source of selenium is the diet (animal and cereal sources) and its intestinal absorption is limiting for selenocysteine and selenomethionine synthesis and incorporation in selenoproteins. In this review, after establishing the link between selenium and inflammatory diseases, we envisaged the potential of selenium nanoparticles and organic selenocompounds to compensate the deficit of selenium intake from the diet. With high selenium loading, nanoparticles offer a low dosage to restore selenium bioavailability whereas organic selenocompounds can play a role in the modulation of their antioxidant or antiinflammatory activities.

Inorganic Polysulfides and Related Reactive Sulfur­Selenium Species from the Perspective of Chemistry.

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.

Microbial transformation of Se oxyanions in cultures of Delftia lacustris grown under aerobic conditions.

Delftia lacustris is reported for the first time as a selenate and selenite reducing bacterium, capable of tolerating and growing in the presence of ≥ 100 mM selenate and 25 mM selenite. The selenate reduction profiles of D. lacustris were investigated by varying selenate concentration, inoculum size, concentration and source of organic electron donor in minimal salt medium. Interestingly, the bacterium was able to reduce both selenate and selenite under aerobic conditions. Although considerable removal of selenate was observed at all concentrations investigated, D. lacustris was able to completely reduce 0.1 mM selenate within 96 h using lactate as the carbon source. Around 62.2% unaccounted selenium (unidentified organo-selenium compounds), 10.9% elemental selenium and 26.9% selenite were determined in the medium after complete reduction of selenate. Studies of the enzymatic activity of the cell fractions show that the selenite/selenate reducing enzymes were intracellular and independent of NADPH availability. D. lacustris shows an unique metabolism of selenium oxyanions to form elemental selenium and possibly also selenium ester compounds, thus a potential candidate for the remediation of selenium-contaminated wastewaters in aerobic environments. This novel finding will advance the field of bioremediation of selenium-contaminated sites and selenium bio-recovery and the production of potentially beneficial organic and inorganic reactive selenium species.

A Comparison of the Antibacterial and Antifungal Activities of Thiosulfinate Analogues of Allicin.

Allicin (diallylthiosulfinate) is a defence molecule from garlic (Allium sativum L.) with broad antimicrobial activities in the low µM range against Gram-positive and -negative bacteria, including antibiotic resistant strains, and fungi. Allicin reacts with thiol groups and can inactivate essential enzymes. However, allicin is unstable at room temperature and antimicrobial activity is lost within minutes upon heating to >80 °C. Allicin's antimicrobial activity is due to the thiosulfinate group, so we synthesized a series of allicin analogues and tested their antimicrobial properties and thermal stability. Dimethyl-, diethyl-, diallyl-, dipropyl- and dibenzyl-thiosulfinates were synthesized and tested in vitro against bacteria and the model fungus Saccharomyces cerevisiae, human and plant cells in culture and Arabidopsis root growth. The more volatile compounds showed significant antimicrobial properties via the gas phase. A chemogenetic screen with selected yeast mutants showed that the mode of action of the analogues was similar to that of allicin and that the glutathione pool and glutathione metabolism were of central importance for resistance against them. Thiosulfinates differed in their effectivity against specific organisms and some were thermally more stable than allicin. These analogues could be suitable for applications in medicine and agriculture either singly or in combination with other antimicrobials.

No time to waste organic waste: Nanosizing converts remains of food processing into refined materials.

Modern food processing results in considerable amounts of side-products, such as grape seeds, walnut shells, spent coffee grounds, and harvested tomato plants. These materials are still rich in valuable and biologically active substances and therefore of interest from the perspective of waste management and "up-cycling". In contrast to traditional, often time consuming and low-value uses, such as vermicomposting and anaerobic digestion, the complete conversion into nanosuspensions unlocks considerable potentials of and new applications for such already spent organic materials without the need of extraction and without producing any additional waste. In this study, nanosuspensions were produced using a sequence of milling and homogenization methods, including High Speed Stirring (HSS) and High Pressure Homogenization (HPH) which reduced the size of the particles to 200-400 nm. The resulting nanosuspensions demonstrated nematicidal and antimicrobial activity and their antioxidant activities exceeded the ones of the bulk materials. In the future, this simple nanosizing approach may fulfil several important objectives, such as reducing and turning readily available waste into new value and eventually closing a crucial cycle of agricultural products returning to their fields - with a resounding ecological impact in the fields of medicine, agriculture, cosmetics and fermentation. Moreover, up-cycling via nanosizing adds an economical promise of increased value to residue-free waste management.

Antibacterial activity and cytotoxicity of Pterocarpus erinaceus Poir extracts, fractions and isolated compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: Pterocarpus erinaceus has been chosen based on ethnobotanical surveys carried out in the Tchamba district of the Republic of Togo. AIM OF THE STUDY: Investigation of the antibacterial as well as cytotoxic activities of whole extracts, fractions and compounds isolated from the leaves, trunk bark and roots of Pterocarpus erinaceus. MATERIALS AND METHODS: Bio-guided fractionation of the raw extracts of plant parts and subsequent isolation of compounds from active fractions using normal phase open column chromatography. The broth microdilution method was used to evaluate the antibacterial activity, based on the determination of Minimal Inhibitory Concentrations (MICs) against several bacterial species representative of the most commonly encountered infectious diseases worldwide. The cytotoxicity of the raw extract and the most active fractions on a human non-cancerous cell (namely MRC-5) was estimated with a MTT assay. The chemical structure of the compounds isolated was elucidated using a combination of advanced Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS). RESULTS: All extracts and fractions tested have shown good activities against Gram-positive bacteria (including Methicillin-Resistant Staphylococcus aureus, MRSA) and against Pseudomonas aeruginosa with MIC values ranging from 32µg/mL to 256µg/mL. In contrast, extracts were not toxic to MRC-5 cells. Four compounds have been isolated: Compound 1 (friedeline); Compound 2 (2,3 dihydroxypropyloctacosanoate); Compound 3 (a mixture of ß-sitosterol, stigmasterol and campesterol); Compound 4 (ß-sitosteryl-ß-D-glucopyranoside) and shown to be active against some of the bacteria tested. They were active with MIC equal to 4µg/mL against strains of S. aureus (including MRSA). To the best of our knowledge, all of them except friedeline have never been reported in this plant species. CONCLUSION: P. erinaceus is confirmed as a plant harboring promising antibacterial activity with activities against serious human pathogens at very low concentrations. Some of the compounds isolated are also active at concentrations as low as 4µg/mL and therefore, may provide new leads for the development of antibacterial agents.

An Optimized Facile Procedure to Synthesize and Purify Allicin.

Allicin is a reactive sulfur species (RSS) and defence substance from garlic (Allium sativum L.). The compound is a broad-spectrum antibiotic that is also effective against multiple drug resistant (MDR) strains. A detailed protocol for allicin synthesis based on diallyl-disulfide (DADS) oxidation by H2O2 using acetic acid as a catalyst was published in 2001 by Lawson and Wang. Here we report on improvements to this basic method, clarify the mechanism of the reaction and show that it is zero-order with respect to DADS and first-order with respect to the concentration of H2O2. The progress of allicin synthesis and the reaction mechanism were analyzsd by high-performance liquid chromatography (HPLC) and the identity and purity of the products was verified with LC-MS and ¹H-NMR. We were able to obtain allicin of high purity (>98%) and >91% yield, with standard equipment available in any reasonable biological laboratory. This protocol will enable researchers to prepare and work with easily and cheaply prepared allicin of high quality.

Nematicidal and antimicrobial activities of methanol extracts of 17 plants, of importance in ethnopharmacology, obtained from the Arabian Peninsula.

AIM/BACKGROUND: The development of resistance to synthetic drugs by target organisms is a major challenge facing medicine, yet locked within plants are phytochemicals used in herbal medicine (especially in the Arabian Peninsula) that may find application in this regard. In pursuit of unlocking these "hidden treasures," the methanol extracts of leaves, aerial parts, fruits, and resins of 17 plants used in the Arabian Peninsula were screened for antimicrobial activities. MATERIALS AND METHODS: The nematicidal, antibacterial, and antifungal activities were determined using appropriate assays. Steinernema feltiae, Staphylococcus carnosus, Escherichia coli, and Saccharomyces cerevisiae were used as test organisms. Concentrations of the extracts ranging from 0.5 to 20 mg/ml were tested and appropriate statistical tests performed on the data generated. RESULTS: The results show that extracts from Solanum incanum, Chenopodium murale, Commiphora myrrha, Anthemis nobilis, and Achillea biebersteinii were the most active and had very high activities against two or more of the test organisms at low concentrations. Extracts of the leaves of S. incanum and resins of Ferula asafoetida were the most active nematicides, with significant activity at 0.5 mg/ml. Extracts of C. myrrha and C. murale had the most active antibacterial activity with inhibition zones of 12-15 mm and minimum inhibitory concentrations (MICs) of 2.5 mg/ml for both bacteria. Extracts of the leaves of A. biebersteinii were the most active fungicide, giving an MIC of 1.5 mg/ml. CONCLUSION: The results validate the use of these plants in ethnopharmacology, and open new vistas of opportunities for the development of cheap but effective agents that may be useful against infectious diseases.

Inspired by Nature: The Use of Plant-derived Substrate/Enzyme Combinations to Generate Antimicrobial Activity in situ.

The last decade has witnessed a renewed interest in antimicrobial agents. Plants have received particular attention and frequently rely on the spontaneous enzymatic conversion of an inactive precursor to an active agent. Such two-component substrate/enzyme defence systems can be reconstituted ex vivo. Here, the alliin/alliinase system from garlic seems to be rather effective against Saccharomyces cerevisiae, whilst the glucosinolate/myrosinase system from mustard appears to be more active against certain bacteria. Studies with myrosinase also confirm that enzyme and substrate can be added sequentially. Ultimately, such binary systems hold considerable promise and may be employed in a medical or agricultural context.