physico-chemical parameter
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POM analysis and related approaches are significant tools based on calculating various physico-chemical properties and predicting biological activity, ADME parameters, and toxicity of a molecule. These methods are used to evaluate a molecule's potential to become a drug candidate. Avenanthramides (AVNs) are promising secondary metabolites specific to Avena spp. (oat). They comprise the amides of anthranilic acid linked to various polyphenolic acids with or without post-condensation molecule transformation. These natural compounds have been reported to exert numerous biological effects, including antioxidant, anti-inflammatory, hepatoprotective, antiatherogenic, and antiproliferative properties. To date, almost 50 various AVNs have been identified. We performed a modified POM analysis of 42 AVNs using MOLINSPIRATION, SWISSADME, and OSIRIS software. The evaluation of primary in silico parameters revealed significant differences among individual AVNs, highlighting the most promising candidates. These preliminary results may help coordinate and initiate other research projects focused on particular AVNs, especially those with predicted bioactivity, low toxicity, optimal ADME parameters, and promising perspectives.
- Publikační typ
- časopisecké články MeSH
Lipid nanocarriers are among the most employed systems for drug delivery purposes in several research and industrial sectors, since their favorable properties ensure broad applicability. The design and characterization of these nanosystems are of paramount importance to obtain controlled outcome, since the supramolecular structure and molecular interactions deeply impact the functionality of the resulting aggregates. The choice of the most appropriate formulation for the target of interest relies on in-depth physico-chemical characterization in order to optimize stability, loading rates and sustained release. Several supramolecular architectures suited for carrier development can be obtained from lipid building blocks, by varying lipid composition and packing parameter. In particular, cubosome and liposome aggregates are often used as drug vectors thanks to their high cargo capability and biocompatibility. Moreover, the possibility to employ lipids from natural sources i.e. biomasses to prepare nanosystems makes them especially attractive. In this work, two aggregate types were characterized and compared as drug vectors for poorly water-soluble antioxidants, particularly curcumin and two adjuvants (i.e. tocopherol and piperine). The nanovectors were obtained by extracting lipids from algal biomasses with different lipid composition, and characterized by advanced structural (DLS, SAXS, Cryo-TEM) techniques, spectroscopy (NMR) and calorimetry (ITC). Finally, the structural stability of both aggregate types was evaluated.
The aim of this study was to determine the influence of syringic acid (SA), a plant secondary metabolite (PSM), on the properties of soil contaminated with 2-methyl-4-chlorophenoxyacetic acid (MCPA) and the condition of two cucurbit species zucchini (C. pepo L. 'Atena Polka') and cucumber (C. sativus 'Cezar') grown on that soil. It was found that amendment with MCPA and MCPA + SA modified the soil physico-chemical properties. Content of N and K was significantly higher for variants amended with SA and/or MCPA, while P content was lower in variant amended with SA. The cucurbits demonstrated varied efficiencies in mitigating the phytotoxicity of the MCPA-treated soil. For soil amended with MCPA + SA, samples remediated with cucumber were characterized as slightly toxic or toxic (45.2%-81.5%), while those planted with zucchini were nontoxic or slightly toxic (-40.6%-47.8%). Development of cucumber seedlings was fully inhibited by MCPA, regardless of SA application, zucchini demonstrated enhanced growth in soil treated with MCPA + SA and no statistically significant differences between morphological parameters of MCPA + SA-treated zucchini in comparison to control plants were observed. The obtained findings suggest that the application of SA is a promising way to mitigate the toxic influence of MCPA in the soil, depending on the cultivated plant species. Novelty statement: The study meets the criteria of novelty and innovativeness. Most importantly, the study is focused on: phytotoxicity studies to inform about the limitations of phytotechnology based on PSMs. Additionally, this manuscript provides an interdisciplinary description of the effects of MCPA and naturally occurring PSM- SA on cucurbits and soil parameters. Such studies, which combine the interactions between cucurbits, their secondary metabolite (SA) and their role in mitigation of phytotoxicity in MCPA-contaminated soil, has not been performed before.
Antimicrobial drug resistance is currently one of the most critical health issues. Pathogens resistant to last-resort antibiotics are increasing, and very few effective antibacterial agents have been introduced in recent years. The promising drug candidates are often discontinued in the primary stages of the drug discovery pipeline due to their unspecific reactivity (PAINS), toxicity, insufficient stability, or low water solubility. In this work, we investigated a series of substituted N-oxazolyl- and N-thiazolylcarboxamides of various pyridinecarboxylic acids. Final compounds were tested against several microbial species. In general, oxazole-containing compounds showed high activity against mycobacteria, especially Mycobacterium tuberculosis (best MICH37Ra = 3.13 μg/mL), including the multidrug-resistant strains. Promising activities against various bacterial and fungal strains were also observed. None of the compounds was significantly cytotoxic against the HepG2 cell line. Experimental measurement of lipophilicity parameter log k'w and water solubility (log S) confirmed significantly (typically two orders in logarithmic scale) increased hydrophilicity/water solubility of oxazole derivatives in comparison with their thiazole isosteres. Mycobacterial β-ketoacyl-acyl carrier protein synthase III (FabH) was suggested as a probable target by molecular docking and molecular dynamics simulations.
- Publikační typ
- časopisecké články MeSH
Liposomes are essentially a subtype of nanoparticles comprising a hydrophobic tail and a hydrophilic head constituting a phospholipid membrane. The spherical or multilayered spherical structures of liposomes are highly rich in lipid contents with numerous criteria for their classification, including structural features, structural parameters, and size, synthesis methods, preparation, and drug loading. Despite various liposomal applications, such as drug, vaccine/gene delivery, biosensors fabrication, diagnosis, and food products applications, their use encounters many limitations due to physico-chemical instability as their stability is vigorously affected by the constituting ingredients wherein cholesterol performs a vital role in the stability of the liposomal membrane. It has well established that cholesterol exerts its impact by controlling fluidity, permeability, membrane strength, elasticity and stiffness, transition temperature (Tm), drug retention, phospholipid packing, and plasma stability. Although the undetermined optimum amount of cholesterol for preparing a stable and controlled release vehicle has been the downside, but researchers are still focused on cholesterol as a promising material for the stability of liposomes necessitating explanation for the stability promotion of liposomes. Herein, the prior art pertaining to the liposomal appliances, especially for drug delivery in cancer therapy, and their stability emphasizing the roles of cholesterol.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Pellets with an immobilized enzyme (acetyl- or butyrylcholinesterase) are the up-to-date type of carriers used for the detection of nerve agents (soman, sarin, tabun, VX, Novichok) and other cholinesterase inhibitors such as organophosphate and carbamate insecticides (parathion, malathion). They are used in the glass detection tubes as a layer containing the enzyme together with the second layer, which contains a colorimetric reagent and substrate. The detection method is based on the visually or spectrophotometrically observable Ellman's reaction, which develops a yellow color in the absence of the cholinesterase inhibitor; otherwise, the detector preserves its original color (preferably white). This reaction occurs very fast and has a high sensitivity to nerve agents but it suffers from an indistinctive color transition from white to yellow. In the presented study, a new approach with the use of the synergic effect of magnesium aluminometasilicate with a high surface area marketed as Neusilin®US2 and a protective semipermeable Eudragit® RL layer was utilized. The prepared pellets have been evaluated for their properties such as the activity of the enzyme, intensity of the developed yellow color, sensitivity to cholinesterase inhibitor physostigmine, which acts as a nerve agent simulant, and physical parameters such as hardness, pycnometric density and sphericity. After the initial evaluation, all samples underwent a stability test under three different storage conditions for 24 months during which they were evaluated at given time points (0, 3, 6, 12 and 24 months). It was found that the prepared samples achieved a much higher intensity of developed yellow color than in the published studies while maintaining similar or better sensitivity, speed of detection and suitable physico-chemical properties.
- MeSH
- acetylcholinesterasa chemie MeSH
- butyrylcholinesterasa chemie MeSH
- časové faktory MeSH
- cholinesterasové inhibitory analýza MeSH
- enzymy imobilizované chemie MeSH
- kolorimetrie metody MeSH
- nervová bojová látka analýza MeSH
- polymery chemie MeSH
- silikáty chemie MeSH
- sloučeniny hliníku chemie MeSH
- sloučeniny hořčíku chemie MeSH
- Publikační typ
- časopisecké články MeSH
The remediation of a soil contaminated with Zn, Pb and Cd was tested by using biochar (BC), nano zero-valent iron (nZVI) and a combination of these two (BC + nZVI). Each amendment was individually applied to the soil at 2 wt%. We tested the influence of (i) the used amendments, (ii) time, and (iii) soil moisture conditions on the metal availability and soil physico-chemical parameters using various extraction methods, as well as soil pore water samplings. We found that metal availability was mainly affected by pH under the influence of time and water content. Among the tested treatments, BC was the most successful, resulting in the lowest amounts of the target metals in the pore water and the smallest temporal changes in metal concentrations and pH in the soil. The use of nZVI efficiently decreased water-extractable Pb in the short- and long-term. The BC + nZVI treatment also yielded promising results regarding the immobilisation of the studied metals. Time provoked a general decrease in pH, which occasionally increased the available metal concentrations. Raising the soil water content increased the pH and subsequently lowered the available metal concentrations in the pore water. The mechanisms of metal stabilisation were further investigated by SEM/EDS. The results indicated that the used soil amendments enhanced the binding of Zn, Pb, and Cd on Fe/Mn/Al oxides/hydroxides, which in turn resulted in the stabilisation of the target metals.
- MeSH
- dřevěné a živočišné uhlí chemie MeSH
- kadmium analýza MeSH
- látky znečišťující půdu analýza chemie MeSH
- olovo MeSH
- oxidy chemie MeSH
- půda chemie MeSH
- regenerace a remediace životního prostředí metody MeSH
- těžké kovy analýza chemie MeSH
- železo chemie MeSH
- zinek analýza MeSH
- Publikační typ
- časopisecké články MeSH
Clearwater Mesa (James Ross Island, northeast Antarctic Peninsula) provides a unique opportunity to study solute dynamics and geochemical weathering in the pristine lacustrine systems of a high latitude environment. In order to determine major controls on the solute composition of these habitats, a geochemical survey was conducted on 35 lakes. Differences between lakes were observed based on measured physico-chemical parameters, revealing neutral to alkaline waters with total dissolved solids (TDS) < 2500 mg L-1. Katerina and Trinidad-Tatana systems showed an increase in their respective TDS, total organic carbon values, and finner sediments from external to internal lakes, indicating an accumulation of solutes due to weathering. Norma and Florencia systems exhibited the most diluted and circumneutral waters, likely from the influence of glacier and snow melt. Finally, isolated lakes presented large variability in TDS values, indicating weathering and meltwater contributions at different proportions. Trace metal abundances revealed a volcanic mineral weathering source, except for Pb and Zn, which could potentially indicate atmospheric inputs. Geochemical modelling was also conducted on a subset of connected lakes to gain greater insight into processes determining solute composition, resulting in the weathering of salts, carbonates and silicates with the corresponding generation of clays. We found CO2 consumption accounted for 20-30% of the total species involved in weathering reactions. These observations allow insights into naturally occurring geochemical processes in a pristine environment, while also providing baseline data for future research assessing the impacts of anthropogenic pollution and the effects of climate change.
- MeSH
- ekosystém MeSH
- geologické sedimenty chemie MeSH
- jezera chemie MeSH
- klimatické změny MeSH
- ledový příkrov chemie MeSH
- minerály analýza MeSH
- monitorování životního prostředí metody MeSH
- olovo analýza MeSH
- organické látky analýza MeSH
- počasí MeSH
- stopové prvky analýza MeSH
- uhličitany analýza MeSH
- zinek analýza MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Antarktida MeSH
- Trinidad a Tobago MeSH
The target diosgenin-betulinic acid conjugates are reported to investigate their ability to enhance and modify the pharmacological effects of their components. The detailed synthetic procedure that includes copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction), and palladium-catalyzed debenzylation by hydrogenolysis is described together with the results of cytotoxicity screening tests. Palladium-catalyzed debenzylation reaction of benzyl ester intermediates was the key step in this synthetic procedure due to the simultaneous presence of a 1,4-disubstituted 1,2,3-triazole ring in the molecule that was a competing coordination site for the palladium catalyst. High pressure (130 kPa) palladium-catalyzed procedure represented a successful synthetic step yielding the required products. The conjugate 7 showed selective cytotoxicity in human T-lymphoblastic leukemia (CEM) cancer cells (IC50 = 6.5 ± 1.1 µM), in contrast to the conjugate 8 showing no cytotoxicity, and diosgenin (1), an adaptogen, for which a potential to be active on central nervous system was calculated in silico. In addition, 5 showed medium multifarious cytotoxicity in human T-lymphoblastic leukemia (CEM), human cervical cancer (HeLa), and human colon cancer (HCT 116). Betulinic acid (2) and the intermediates 3 and 4 showed no cytotoxicity in the tested cancer cell lines. The experimental data obtained are supplemented by and compared with the in silico calculated physico-chemical and absorption, distribution, metabolism, and excretion (ADME) parameters of these compounds.
- MeSH
- cykloadiční reakce MeSH
- diosgenin chemie MeSH
- hydrogenace MeSH
- katalýza MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- palladium chemie MeSH
- pentacyklické triterpeny chemie MeSH
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- tlak MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Karst rivers are of great interest for commercial fishing and aquaculture, yet they are quite vulnerable aquatic environments because the permeable karst rocks do not effectively filter out contaminants. To understand the current state of karst rivers water quality, we analysed the physico-chemical and microbiological parameters, focusing on antibiotic pollution and the emergence of antibiotic-resistant microbes of three such rivers in Croatia. Water quality varied between classes I and II across sampling sites, and the numbers of total coliforms, enterococci and heterotrophic bacteria varied substantially among sites. Swabs from fish gills, spleen, liver and kidneys were cultured and 94 isolates identified by MALDI-TOF mass spectrometry. The predominant genus was Aeromonas (42.5% of all identified isolates), known for its adaptability to polluted environments and its frequent association with antibiotic resistance. Of the selected Aeromonas isolates known as most pathogenic, half were resistant to at least three antibiotic categories. The Enterobacteriaceae family was represented by the greatest number of genera, most of which are pathogenic for humans and animals and are spoilage bacteria for fish. The results of this study highlight the extent of antibiotic contamination in aquatic environments and the increasing threat of pathogenic and spoilage bacteria in traditionally high-quality karst rivers.
- MeSH
- Aeromonas * genetika MeSH
- antibakteriální látky farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- řeky * MeSH
- voda MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Černé moře MeSH
- Chorvatsko MeSH
