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•Esters of 1,2-ethane and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid.•Gastrointestinal absorption and membrane retention were predicted using PAMPA.•Membrane retention ...is in correlation with previous results of cytotoxic activity.•QSPR and QSRR analyses were performed.•New derivatives with favourable absorption and retention properties were designed.
Passive gastrointestinal absorption and membrane retention of twelve esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP), as well as of these two non-esterified acids were estimated using PAMPA test. Artificial PAMPA membrane used in this study for the simulation of gastrointestinal barrier was solution of egg lecithin in dodecane (1 % w/v). All tested compounds belong to class III (high membrane retention and low permeation), whereas EDCP, dipentyl ester of PDCP (DPE-PDCP) and diisopentyl ester of PDCP (DIPE-PDCP) belong to class I (negligible membrane retention and low permeation). Finally, quantitative structure – permeability and structure – retention relationships models were created in order to find quantitative relationships between physico-chemical properties of tested compounds and PAMPA membrane permeability/membrane retention parameters. Statistically the most reliable models were analysed and used for the design of new compounds for which favourable membrane permeability and retention can be expected.
The pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example, Marek's disease virus (MDV), ...which causes lymphoid tumors in chickens, has experienced a marked increase in virulence over the past century. Today, MDV infections kill >90% of unvaccinated birds, and controlling it costs more than US$1 billion annually. By sequencing MDV genomes derived from archeological chickens, we demonstrate that it has been circulating for at least 1000 years. We functionally tested the
oncogene, one of 49 viral genes positively selected in modern strains, demonstrating that ancient MDV was likely incapable of driving tumor formation. Our results demonstrate the power of ancient DNA approaches to trace the molecular basis of virulence in economically relevant pathogens.
The aim of this work was to give more accurate insight in the interaction of
major photosynthesis pigment, chlorophyll (Chl), with copper (II) and zinc
(II) in solution by flow injection analysis ...with electrospray ionization mass
spectrometry (FIA-ESI-MS) method, as well as combined with ultra high
performance liquid chromatography with DAD detection (UHPLC-DAD). These
interactions may potentially, but not necessarily lead to formation of Cu-Chl
and Zn-Chl complexes of two different types, which has a lot of - at least -
disfunctional implications in plant world. The results based on analysis of
full-scan and MS/MS spectra - with or without the UHPLC chromatograms -
confirm formation of ?central type? Cu-Chl complex, and ?central type? Zn-Chl
complex as well, along with a proof for formation of ?peripheral? Zn-Chl
complex, the latter one originating from a very week coordinative interaction
at the edge of Chl structure. The used techniques appeared to be an efficient
and reliable tool for studying formation and stability of heavy metals
complexes with chlorophyll, at least in vitro, with a considerable
possibility for assessment of real bio-environmental behavior.
Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs. The need is justified by the ...fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects.
Eight β-hydroxy-β-arylpropanoic acids, which belong to the arylpropanoic acid class of compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Seven out of those eight acids were synthesized using already published modification of Reformatsky reaction additionally optimized by increasing temperature. Synthesized compounds were tested in vivo in order to elucidate anti-inflammatory activity, gastric tolerability and impact on liver function of rats.
Results of docking studies have indicated that all compounds have potential to selectively inhibit COX-2 isoform, but that the compounds containing polar substituents on phenyl ring are better inhibitors. Results of carrageenan-induced rat paw oedema test have shown that all compounds exhibit dose dependence and good gastric tolerability and none of the tested compounds have shown negative effect on liver function compared to ibuprofen.
The compound containing polar nitro group in para position has shown the best docking results, anti-inflammatory activity, low hepatotoxicity and good gastric tolerability.
As the number of poorly soluble drugs is increasing, nanocrystals have become very interesting due to wide range of application possibilities. Curcuminwas used as a model active ingredient in this ...work. Even though it has many proven positive effects, due to its physicochemical issues, its possibilities have not been fully exploited. The goal of this work was to select optimal conditions for a top-down method for curcumin nanosuspension production, and to perform their comprehensive characterization applying complementary methodologies: dynamic light scattering, polarization and atomic force microscopy, thermal analysis, X-ray powder diffraction, antioxidant activity evaluation, release kinetics assessment, and screening of potential biological effects applying cell viability assays on normal human lung fibroblasts, human melanoma and human adenomacarcinoma cells. After 30 min of milling, nanosuspensions stabilized by polysorbate 80 and by its combinations with sucrose palmitate showed good stability, while curcumin crystal structure was unaltered. Obtained nanocrystals were well defined, with average diameter 120–170 nm and PDI of about 0.25, zeta potential was below −30 mV and pH~5 for all formulations. Nanodispersions exhibited high antioxidant potential and improved dissolution rate compared to the corresponding coarse dispersions. Although curcumin nanodispersions exhibited significant antiproliferative effect to each cancer cell line, the highest effect was towards adenocarcinoma cells.
The antioxidant activity of cynodontin was studied in the absence and the presence of free radical species. This in silico study was performed in water and benzene, with the aim to simulate polar and ...non-polar environment. To determine the most probable mechanism of antioxidant action, density functional theory (DFT) was employed. The change in reaction enthalpy of cynodontin with three different free radicals (hydroxyl, hydroperoxyl, and methyl peroxyl radical) were examined and presented. SET-PT (Single Electron Transfer – Proton Transfer) mechanism is not an operative mechanism of antioxidant action. The obtained results imply that the possible mechanism of antioxidant action in water is SPLET (Sequential Proton Loss Electron Transfer), while in benzene HAT (Hydrogen atom transfer) and SPLET are competitive mechanisms. The molecular docking study was performed in order to estimate the inhibition potency of the investigated compound toward human leukocyte elastase (HLE). The obtained results indicate that numerous interactions determine the inhibition activity towards the investigated protein.
Eco-friendly and rapid microwave processing of a precipitate was used to produce Fe-doped zinc oxide (Zn
1−x
Fe
x
O,
x
= 0, 0.05, 0.1, 0.15 and 0.20; ZnO:Fe) nanoparticles, which were tested as ...catalysts toward the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in a moderately alkaline solution. The phase composition, crystal structure, morphology, textural properties, surface chemistry, optical properties and band structure were examined to comprehend the influence of Zn
2+
partial substitution with Fe
3+
on the catalytic activity of ZnO:Fe. Linear sweep voltammetry showed an improved catalytic activity of ZnO:5Fe toward the ORR, compared to pure ZnO, while with increased amounts of the Fe-dopant the activity decreased. The improvement was suggested by a more positive onset potential (0.394 V
vs.
RHE), current density (0.231 mA cm
−2
at 0.150 V
vs.
RHE), and faster kinetics (Tafel slope,
b
= 248 mV dec
−1
), and it may be due to the synergistic effect of (1) a sufficient amount of surface oxygen vacancies, and (2) a certain amount of plate-like particles composed of crystallites with well developed (0001) and (0001̄) facets. Quite the contrary, the OER study showed that the introduction of Fe
3+
ions into the ZnO crystal structure resulted in enhanced catalytic activity of all ZnO:Fe samples, compared to pure ZnO, probably due to the modified binding energy and an optimized band structure. With the maximal current density of 1.066 mA cm
−2
at 2.216 V
vs.
RHE, an onset potential of 1.856 V
vs.
RHE, and the smallest potential difference between the OER and ORR (Δ
E
= 1.58 V), ZnO:10Fe may be considered a promising bifunctional catalyst toward the OER/ORR in moderately alkaline solution. This study demonstrates that the electrocatalytic activity of ZnO:Fe strongly depends on the defect chemistry and consequently the band structure. Along with providing fundamental insight into the electrocatalytic activity of ZnO:Fe, the study also indicates an optimal stoichiometry for enhanced bifunctional activity toward the OER/ORR, compared to pure ZnO.
Even though structural elements of the elliptical hollow section (EHS) have been introduced to the construction market in the past years, the rules for their design were only partially introduced ...into the suitable codified procedures. The aim of this paper is to present a comparative numerical analysis of behaviour of coldformed and hot-finished EHS columns exposed to flexural buckling under pure axial compression. Pinended columns of a various slenderness without lateral restrains and with incorporated geometrical imperfections are analysed. Material nonlinear behaviour is included through published experimental tensile test results, conducted in previous researches. In addition, numerical simulations of stub column behaviour are performed in order to obtain a cross-section compressive resistance. Results of the finite element analysis are compared to the design criteria defined in the draft version of Eurocode EN 1993-1-1:2015 and in North American specification for cold-formed member design AISI-S100. It is observed that North American standard provides more accurate predictions of both a crosssection resistance and a buckling column resistance. Equivalent diameter method described in Eurocode 3 led to more conservative results. According to the obtained numerical results, similar buckling behaviour is observed for both hot-finished and cold-formed columns of higher slenderness, while in the lower slenderness region, coldformed compressed members tend to lower buckling curves. Underestimation of a column buckling resistance according to Eurocode regulations is noticed for coldformed members of a higher slenderness.
Dental caries is one of the most prevalent public health problems. It is caused by a well-organized bacterial structure i.e. , biofilm, where the cariogenic bacteria Streptococcus mutans is ...recognized as the primary pathogenic factor. Furthermore, the first phase of dental biofilm onset is predominantly associated to bacteria of the Streptococcus genus. This research aimed to assess the antibacterial and antibiofilm potential of monoterpene carvacrol, against relevant tooth caries-associated isolates, including Streptococcus mutans , Streptococcus sanguinis , Streptococcus mitis , and Streptococcus gordonii . Microdilution test was used for the assessment of the antimicrobial potential of carvacrol, and the minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined. The capacity of carvacrol to disrupt pre-formed biofilm and prevent its formation was evaluated in crystal violet assay. Tested monoterpene achieved notable antimicrobial activity, with MICs ranging from 1.22 mg mL -1 to 2.44 mg mL -1 , and MBCs from 1.22 mg mL -1 to 19.52 mg mL -1 . Screening of the prevention of biofilm biomass formation revealed that carvacrol has the potential to prevent biofilm formation of the S. sanguinis , S. gordoni i (41% and 47% of inhibition, at concentration 4.88 mg mL -1 respectively) and S. mutans (at higher tested concentrations 59% of inhibition, at concentration of 19.52 mg mL -1 ). Biofilm disruption also occurred in case of S. mitis and S. sanguinis biofilms (40% and 46% of biomass decrease, respectively, at concentration of 2.44 mg mL -1 ). According to the study results, carvacrol could be valuable as an active antibacterial agent and incorporated in adjunct to oral hygiene maintenance.
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