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1.
Front Nutr ; 11: 1325190, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38769990

RESUMO

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.

2.
J Med Chem ; 67(2): 1580-1610, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38190615

RESUMO

Alzheimer's disease (AD) has a complex and not-fully-understood etiology. Recently, the serotonin receptor 5-HT6 emerged as a promising target for AD treatment; thus, here a new series of 5-HT6R ligands with a 1,3,5-triazine core and selenoether linkers was explored. Among them, the 2-naphthyl derivatives exhibited strong 5-HT6R affinity and selectivity over 5-HT1AR (13-15), 5-HT7R (14 and 15), and 5-HT2AR (13). Compound 15 displayed high selectivity for 5-HT6R over other central nervous system receptors and exhibited low risk of cardio-, hepato-, and nephrotoxicity and no mutagenicity, indicating its "drug-like" potential. Compound 15 also demonstrated neuroprotection against rotenone-induced neurotoxicity as well as antioxidant and glutathione peroxidase (GPx)-like activity and regulated antioxidant and pro-inflammatory genes and NRF2 nuclear translocation. In rats, 15 showed satisfying pharmacokinetics, penetrated the blood-brain barrier, reversed MK-801-induced memory impairment, and exhibited anxiolytic-like properties. 15's neuroprotective and procognitive-like effects, stronger than those of the approved drug donepezil, may pave the way for the use of selenotriazines to inhibit both causes and symptoms in AD therapy.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Selênio , Ratos , Animais , Doença de Alzheimer/tratamento farmacológico , Serotonina/uso terapêutico , Ratos Wistar , Neuroproteção , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Receptores de Serotonina , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
3.
Curr Opin Chem Biol ; 76: 102365, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37463529

RESUMO

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.


Assuntos
Compostos de Selênio , Selênio , Selênio/química , Oxirredução , Compostos de Selênio/metabolismo , Fermentação
4.
Antibiotics (Basel) ; 12(2)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36830201

RESUMO

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.

5.
Antibiotics (Basel) ; 11(10)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36290073

RESUMO

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.

6.
Antioxidants (Basel) ; 11(6)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35739933

RESUMO

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.

7.
Drug Resist Updat ; 63: 100844, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35533630

RESUMO

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.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Selênio , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio , Selênio/química , Selênio/farmacologia , Selênio/uso terapêutico , Telúrio/química , Telúrio/farmacologia , Telúrio/uso terapêutico
8.
Food Funct ; 13(9): 5327-5342, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35446320

RESUMO

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.


Assuntos
Ingredientes de Alimentos , Animais , Antioxidantes/análise , Biomarcadores , Células CACO-2 , Fibras na Dieta , Digestão , Grão Comestível/química , Flavonoides , Alimento Funcional , Humanos , Inflamação , Intestino Delgado/química , Estresse Oxidativo , Fenóis/análise
9.
Artigo em Inglês | MEDLINE | ID: mdl-34948512

RESUMO

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.


Assuntos
COVID-19 , Pandemias , Vacinas contra COVID-19 , Controle de Doenças Transmissíveis , Estudos Transversais , Gana/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , SARS-CoV-2 , Inquéritos e Questionários
10.
Antioxidants (Basel) ; 10(8)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34439533

RESUMO

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.

11.
Antioxidants (Basel) ; 10(6)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072794

RESUMO

Selenium is an essential trace element. Although this chalcogen forms a wide variety of compounds, there are surprisingly few small-molecule organic selenium compounds (OSeCs) in biology. Besides its more prominent relative selenocysteine (SeCys), the amino acid selenomethionine (SeMet) is one example. SeMet is synthesized in plants and some fungi and, via nutrition, finds its way into mammalian cells. In contrast to its sulfur analog methionine (Met), SeMet is extraordinarily redox active under physiological conditions and via its catalytic selenide (RSeR')/selenoxide (RSe(O)R') couple provides protection against reactive oxygen species (ROS) and other possibly harmful oxidants. In contrast to SeCys, which is incorporated via an eloquent ribosomal mechanism, SeMet can enter such biomolecules by simply replacing proteinogenic Met. Interestingly, eukaryotes, such as yeast and mammals, also metabolize SeMet to a small family of reactive selenium species (RSeS). Together, SeMet, proteins containing SeMet and metabolites of SeMet form a powerful triad of redox-active metabolites with a plethora of biological implications. In any case, SeMet and its family of natural RSeS provide plenty of opportunities for studies in the fields of nutrition, aging, health and redox biology.

12.
J Environ Sci (China) ; 101: 72-86, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33334539

RESUMO

Intensive agriculture activities, industrialization and growing numbers of wastewater treatment plants along river banks collectively contribute to the elevated levels of neurotoxic pollutants in natural water reservoirs across Europe. We established an in vitro bioassay based upon neural stem cells isolated from the subventricular zone of the postnatal mouse to evaluate the neurotoxic potential of raw wastewater, treated sewage effluent, groundwater and drinking water. The toxic potential of water samples was evaluated employing viability, proliferation, differentiation and migration assays. We found that raw wastewater could reduce the viability and proliferation of neural stem cells, and decreased the neuronal and astrocyte differentiation, neuronal neurite growth, astrocyte growth and cell migration. Treated sewage water also showed inhibitory effects on cell proliferation and migration. Our results indicated that relatively high concentrations of nitrogenous substances, pesticides, mercuric compounds, bisphenol-A, and phthalates, along with some other pollutants in raw wastewater and treated sewage water, might be the reason for the neuroinhibitory effects of these water samples. Our model successfully predicted the neurotoxicity of water samples collected from different sources and also revealed that the incomplete removal of contaminants from wastewater can be problematic for the developing nervous system. The presented data also provides strong evidence that more effective treatments should be used to minimize the contamination of water before release into major water bodies which may be considered as water reservoirs for human usage in the future.


Assuntos
Células-Tronco Neurais , Poluentes Químicos da Água , Animais , Bioensaio , Monitoramento Ambiental , Camundongos , Células-Tronco Neurais/química , Esgotos/análise , Águas Residuárias , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
13.
Environ Pollut ; 270: 116179, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33348142

RESUMO

The developing nervous system is highly vulnerable to environmental toxicants especially pesticides. Glyphosate pesticide induces neurotoxicity both in humans and rodents, but so far only when exposed to higher concentrations. A few studies, however, have also reported the risk of general toxicity of glyphosate at concentrations comparable to allowable limits set up by environmental protection authorities. In vitro data regarding glyphosate neurotoxicity at concentrations comparable to maximum permissible concentrations in drinking water is lacking. In the present study, we established an in vitro assay based upon neural stem cells (NSCs) from the subventricular zone of the postnatal mouse to decipher the effects of two maximum permissible concentrations of glyphosate in drinking water on the basic neurogenesis processes. Our results demonstrated that maximum permissible concentrations of glyphosate recognized by environmental protection authorities significantly reduced the cell migration and differentiation of NSCs as demonstrated by the downregulation of the expression levels of the neuronal ß-tubulin III and the astrocytic S100B genes. The expression of the cytoprotective gene CYP1A1 was downregulated whilst the expression of oxidative stresses indicator gene SOD1 was upregulated. The concentration comparable to non-toxic human plasma concentration significantly induced cytotoxicity and activated Ca2+ signalling in the differentiated culture. Our findings demonstrated that the permissible concentrations of glyphosate in drinking water recognized by environmental protection authorities are capable of inducing neurotoxicity in the developing nervous system.


Assuntos
Água Potável , Herbicidas , Células-Tronco Neurais , Animais , Água Potável/análise , Glicina/análogos & derivados , Glicina/toxicidade , Herbicidas/análise , Ventrículos Laterais/química , Camundongos , Células-Tronco Neurais/química , Glifosato
14.
Pharmaceuticals (Basel) ; 13(12)2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322409

RESUMO

Multidrug resistance of cancer cells to cytotoxic drugs still remains a major obstacle to the success of chemotherapy in cancer treatment. The development of new drug candidates which may serve as P-glycoprotein (P-gp) efflux pump inhibitors is a promising strategy. Selenium analogues of natural products, such as flavonoids, offer an interesting motif from the perspective of drug design. Herein, we report the biological evaluation of novel hybrid compounds, bearing both the flavone core (compounds 1-3) or a bioisosteric analogue core (compounds 4-6) and the triflyl functional group against Gram-positive and Gram-negative bacteria, yeasts, nematodes, and human colonic adenocarcinoma cells. Results show that these flavones and analogues of flavones inhibited the activity of multidrug resistance (MDR) efflux pump ABCB1 (P-glycoprotein, P-gp). Moreover, the results of the rhodamine 123 accumulation assay demonstrated a dose-dependent inhibition of the abovementioned efflux pump. Three compounds (4, 5, and 6) exhibited potent inhibitory activity, much stronger than the positive control, verapamil. Thus, these chalcogen bioisosteric analogues of flavones become an interesting class of compounds which could be considered as P-gp efflux pump inhibitors in the therapy of MDR cancer. Moreover, all the compounds served as promising adjuvants in the cancer treatment, since they exhibited the P-gp efflux pump modulating activity.

15.
AMB Express ; 10(1): 162, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32889670

RESUMO

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.

16.
Free Radic Res ; 53(sup1): 1153-1162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31510813

RESUMO

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.


Assuntos
Antioxidantes/metabolismo , Plantas/metabolismo , Radicais Livres/metabolismo , Homeostase , Oxirredução , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo
17.
Eur J Med Chem ; 178: 740-751, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31229876

RESUMO

This research has provided the most active 5-HT6R agents among 1,3,5-triazine derivatives investigated to date and has also identified the world's first selenium-containing 5-HT6R ligands. The studies are focused on design, synthesis, biological evaluation and docking-supported SAR analysis for novel 5-HT6R agents as derivatives of lead structure 4-(4-methylpiperazin-1-yl)-6-(phenoxymethyl)-1,3,5-triazin-2-amine (7). The lead modifications included an introduction of: (i) various small substituents at benzene ring, (ii) a branched ether linker or (iii) the ether oxygen replacement with other chalcogen (S, Se) or sulfonyl moiety. Hence, a series of new compounds (7-24) was synthesized and examined on their affinities for 5-HT6R and selectivity, in respect to the 5-HT1AR, 5-HT2AR, 5-HT7R and dopamine D2 receptor, in the radioligand binding assays. For representative most active compounds functional bioassays and toxicity profile in vitro and antidepressant-like activity in vivo were examined. The 2-isopropyl-5-methylphenyl derivative (10) was found as the most active triazine 5-HT6R antagonist (Ki = 11 nM). SAR analysis indicated, that an exchange of oxygen to selenium (7 vs. 22), and especially, to sulfur (7 vs. 19) was beneficial to increase both affinity and antagonistic action for 5-HT6R. Surprisingly, an introduction of SO2 caused a drastic decrease of the 5-HT6R affinity, which was explained at a molecular level based on docking studies. All in vivo tested compounds (10, 18 and 21) did not show any risk of toxicity in the safety studies in vitro.


Assuntos
Processamento de Imagem Assistida por Computador , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , Animais , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Ligantes , Locomoção/efeitos dos fármacos , Modelos Moleculares , Estrutura Molecular , Ratos , Antagonistas da Serotonina/síntese química , Antagonistas da Serotonina/química , Relação Estrutura-Atividade
18.
Molecules ; 24(7)2019 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-30959902

RESUMO

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.


Assuntos
Selênio/química , Sulfetos/química , Enxofre/química , Sulfeto de Hidrogênio/química , Nanopartículas/química , Oxirredução , Análise Espectral , Compostos de Enxofre/química
19.
Antioxidants (Basel) ; 7(4)2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29677095

RESUMO

Nanosizing represents a straight forward technique to unlock the biological activity of complex plant materials. The aim of this study was to develop herbal nanoparticles with medicinal value from dried leaves and stems of Loranthus micranthus with the aid of ball-milling, high speed stirring, and high-pressure homogenization techniques. The milled nanoparticles were characterized using laser diffraction analysis, photon correlation spectroscopy analysis, and light microscopy. The average size of leaf nanoparticles was around 245 nm and that of stem nanoparticles was around 180 nm. The nanoparticles were tested for their antimicrobial and nematicidal properties against a Gram-negative bacterium Escherichia coli, a Gram-positive bacterium Staphylococcus carnosus, fungi Candida albicans and Saccharomyces cerevisiae, and a nematode Steinernemafeltiae. The results show significant activities for both leaf and (particularly) stem nanoparticles of Loranthus micranthus on all organisms tested, even at a particle concentration as low as 0.01% (w/w). The results observed indicate that nanoparticles (especially of the stem) of Loranthus micranthus could serve as novel antimicrobial agents with wide-ranging biomedical applications.

20.
Antioxidants (Basel) ; 7(2)2018 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-29382037

RESUMO

Many organic sulfur, selenium and tellurium compounds show considerable activity against microorganisms, including bacteria and fungi. This pronounced activity is often due to the specific, oxidizing redox behavior of the chalcogen-chalcogen bond present in such molecules. Interestingly, similar chalcogen-chalcogen motifs are also found in the elemental forms of these elements, and while those materials are insoluble in aqueous media, it has recently been possible to unlock their biological activities using naturally produced or homogenized suspensions of respective chalcogen nanoparticles. Those suspensions can be employed readily and often effectively against common pathogenic microorganisms, still their practical uses are limited as such suspensions are difficult to transport, store and apply. Using mannitol as stabilizer, it is now possible to lyophilize such suspensions to produce solid forms of the nanoparticles, which upon resuspension in water essentially retain their initial size and exhibit considerable biological activity. The sequence of Nanosizing, Lyophilization and Resuspension (NaLyRe) eventually provides access to a range of lyophilized materials which may be considered as easy-to-handle, ready-to-use and at the same time as bioavailable, active forms of otherwise insoluble or sparingly substances. In the case of elemental sulfur, selenium and tellurium, this approach promises wider practical applications, for instance in the medical or agricultural arena.

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