7348 research outputs found
Sort by
Computational modelling of detected persistent organic pollutants in adriatic pelagic fish: molecular and toxicokinetic perspectives for human health risk assessment
No full textIn this study, an integrative computational approach combining molecular descriptors, genetic algorithm – multiple linear regression (GA–MLR), and toxicokinetic simulations was employed to characterize the preliminary profile of Persistent Organic Pollutants (POPs) in various pelagic fish species from the Adriatic Sea. The molecular basis and toxicokinetic profile based on previously obtained experimental data on POP concentrations were followed by preliminary environmental characterization to assess the relationship between fish-specific parameters (e.g. species, lipid content) and determined pollutant concentrations. A GA coupled with MLR was applied to develop predictive models identifying the most influential physico-chemical properties of POPs that contribute to non-carcinogenic and carcinogenic health risks associated with chronic fish consumption. The toxicokinetic modelling and Hansen solubility parameters (HSPs) were used to assess the consumers’ risk, gastrointestinal absorption and bioaccumulation. The use of GA–MLR and 3D–MoRSE descriptors directly linked chemical structure to environmental fate, bioaccumulation, and toxicological outcomes. The modelled concentrations of POPs in key organs and tissues were compared to in vivo data reported in the literature. This integrated analysis establishes a scientific basis for future toxicological and risk assessments of POPs in Adriatic pelagic fish, with emphasis on experimental validation and toxicokinetic profiling relevant to human exposure
Lacto-fermentation enhances antioxidant and digestive enzyme inhibitory activity of Cotinus coggygria leaf extracts
No full textCotinus coggygria Scop., commonly referred to as the smoke tree or smoke bush (Anacardiaceae), is a medicinal plant with a wide range of therapeutic benefits, such as hepatoprotective, anti-inflammatory, antioxidant, antibacterial, antiviral, anticancer, and antigenotoxic effects [1]. Through modulating enzyme inhibition, boosting antioxidant and antibacterial activity, and improving phytochemical bioavailability, lacto-fermentation further expands the therapeutic potential of plant extracts [2]. This study aims to investigate the impact of lacto-fermentation on the antioxidant activity and digestive enzyme inhibitory activity of Cotinus coggygria leaf extracts. Fermentation-induced changes in the antioxidant profile were clearly observed using the high-performance thin-layer chromatography (HPTLC)-DPPH bioautographic approach. The bioactivity of both fermented and non-fermented ethyl acetate extracts was further assessed through spectrofotometric assays targeting the inhibition of key digestive enzymes, specifically pancreatic lipase and α-amylase. Using a moderately polar mobile phase (n-hexane: ethyl acetate: formic acid: water, 13:9:1:0.5), the HPTLC-DPPH assay showed stronger antioxidant activity in the fermented ethyl acetate extract, with intense yellow zones indicating an increased presence of active phenolic compounds due to fermentation. Fermented ethyl acetate extract of C. coggygria exhibited potent lipase inhibitory activity, comparable to orlistat, suggesting that lacto-fermentation enhances the formation or bioavailability of active constituents. While α-amylase inhibition by C. coggygria has been scarcely reported, our results indicate a significantly higher inhibitory potential in regional samples. Our results demonstrate the plant’s therapeutic potential in managing obesity-related metabolic disorders and warrant further bioactivity-guided molecular investigations, while also revealing that fermentation enhances the bioactivity of smoke tree leaves.Apstrakt: [https://cherry.chem.bg.ac.rs/handle/123456789/7513
Lacto-fermentation enhances antioxidant and digestive enzyme inhibitory activity of Cotinus coggygria leaf extracts
No full textCotinus coggygria Scop., commonly referred to as the smoke tree or smoke bush (Anacardiaceae), is a medicinal plant with a wide range of therapeutic benefits, such as hepatoprotective, anti-inflammatory, antioxidant, antibacterial, antiviral, anticancer, and antigenotoxic effects [1]. Through modulating enzyme inhibition, boosting antioxidant and antibacterial activity, and improving phytochemical bioavailability, lacto-fermentation further expands the therapeutic potential of plant extracts [2]. This study aims to investigate the impact of lacto-fermentation on the antioxidant activity and digestive enzyme inhibitory activity of Cotinus coggygria leaf extracts. Fermentation-induced changes in the antioxidant profile were clearly observed using the high-performance thin-layer chromatography (HPTLC)-DPPH bioautographic approach. The bioactivity of both fermented and non-fermented ethyl acetate extracts was further assessed through spectrofotometric assays targeting the inhibition of key digestive enzymes, specifically pancreatic lipase and α-amylase. Using a moderately polar mobile phase (n-hexane: ethyl acetate: formic acid: water, 13:9:1:0.5), the HPTLC-DPPH assay showed stronger antioxidant activity in the fermented ethyl acetate extract, with intense yellow zones indicating an increased presence of active phenolic compounds due to fermentation. Fermented ethyl acetate extract of C. coggygria exhibited potent lipase inhibitory activity, comparable to orlistat, suggesting that lacto-fermentation enhances the formation or bioavailability of active constituents. While α-amylase inhibition by C. coggygria has been scarcely reported, our results indicate a significantly higher inhibitory potential in regional samples. Our results demonstrate the plant’s therapeutic potential in managing obesity-related metabolic disorders and warrant further bioactivity-guided molecular investigations, while also revealing that fermentation enhances the bioactivity of smoke tree leaves.Poster: [https://cherry.chem.bg.ac.rs/handle/123456789/7504
Synthesis and antinociceptive activity of long-known but unexplored nitro-fentanyl derivatives
No full textFentanyl and related 4-anilidopiperidines are the most potent and clinically important analgesics for the treatmentof severe acute and chronic pain. Many fentanyl derivatives have been made so far to obtain new analgesicswith improved pharmacological profile. However, of simple nitro fentanyl derivatives only the meta isomer wasreported, while ortho and para isomers proved to be synthetically challenging. We report here for the first timethe synthesis of ortho and para-nitro-fentanyl. The most arduous step in the synthesis was the acylation ofnitroaniline precursor, where the ortho and para positioned nitro group with strong electron-withdrawing and/orsteric effects led to an extremely low nucleophilicity of anilino nitrogen. To address this problem electrophilicconditions had to be enhanced using strong acylating agent i.e. propionyl chloride or bromide, and bases such asEt3N or pyridine in a polar, aprotic solvent such as N,N-dimethylformamide (DMF). Indeed, under these conditions,acylation step afforded title products in excellent yields. The in vivo pharmacological evaluationdemonstrated that regioisomerism plays a role in the potency and the onset of action of these compounds. Theortho-nitro derivative emerged as the most effective analgesic, exhibiting approximately 50 times less potencythan fentanyl, comparable to morphine. Furthermore, it demonstrated a faster onset of action than fentanyl whilemaintaining a similar duration of effect. These traits indicate that it may be well-suited for treating severe acutepain and breakthrough pain in chronic pain conditions. Ortho-nitro fentanyl is henceforth worthy of furtherevaluation in toxicity and safety pharmacology studies
Efekti PFOA i PFOS na osetljivost sojeva Pseudomonas prema streptomicinu
No full textZagađenje PFAS jedinjenjima danas je široko rasprostranjeno u životnoj sredini i predstavlja globalni problem. Studije pokazuju da PFOA i PFOS utiču na bakterijsku fiziologiju izazivanjem oksidativnog stresa, oštećenjem membrana, povećanjem permeabilnosti i stimulacijom sekrecije vanćelijskih polimera. Ove promene olakšavaju međućelijski kontakt i transfer plazmida sa ARG genima čime PFAS jedinjenja, pored toksičnih efekata, mogu doprineti širenju antimikrobne rezistencije. U okviru ovog rada ispitan je uticaj PFOA i PFOS na osetljivost na streptomicin tri različita soja Pseudomonas. Rezultati doprinose razumevanju uloge ovih jedinjenja u razvoju rezistencije i ukazuju na potencijalne mehanizme odbrane koji se aktiviraju u prisustvu PFAS kod mikroorganizama što može doprineti boljem razumevanju procesa koji ova jedinjenja imaju na životnu sredinu
Computational Rational Design of Bridgehead Nitrogen Heterocyclic Azobenzene Photoswitches
No full textAzobenzenes are proven to be one of the most successful molecular photoswitches applied across different fields such as organic chemistry, materials science, cosmetics, and pharmaceuticals. Such a widespread implementation is possible because of their photochromic properties contingent upon the substitution pattern and aryl-core nature. In recent endeavors of molecular design, replacing one or both phenyl rings with heteroaromatics turned out to be a good strategy to access compounds with improved photoswitching properties, as well as to expand molecular diversity. One of the challenges related to the design of new azobenzene photoswitches is that it often includes the synthesis of large libraries of compounds due to limited methods for prediction of their properties. Herein, we present a computationally driven workflow for the design and synthesis of a novel class of azobenzene photoswitches, heteroaryl azobenzenes with N-bridgehead heterocycles─pyrazolo[1,5-a]pyrimidine and 1,2,4-triazolo[1,5-a]pyrimidine. A small library of heteroaryl photoswitches was synthesized, and their photochemical properties were evaluated. Subsequently, these results were used to validate a computational approach, which included the in silico evaluation of a large library of designed photoswitch candidates leading to the synthesis of a new photoswitch with improved spectral properties, red-shifted λmax values
Polydisperse Pt Deposits Over TiO2-Nanotube-Array-Supported Ru Nanoparticles: Harnessing the Interfacial Synergy for Efficient Hydrogen Evolution Electrocatalysis
No full textDeveloping cost-effective precious metal electrocatalysts for the hydrogen evolution reaction (HER) is key to realizing the economic viability of acidic water electrolysis. Herein, galvanic displacement is employed for in situ formation of bimetallic Pt/Ru deposits on H-intercalated TiO2 nanotube arrays. It is found that a two-step procedure yields polydisperse deposits with a dominant fraction of Ru nanoparticles coated with atomic and subnanometric Pt islands. These Pt|Ru nanointerfaces induce charge transfer from Pt to Ru, which modulates the electronic structure of Pt sites for accelerated HER kinetics. By varying the platinization time in the second step, a balance between the exposure of catalytically active Pt|Ru nanointerfaces and the total number of Pt surface sites is achieved. The optimized composite, termed Ru-30min@Pt-30min, requires an overpotential of 58 mV to deliver a current density of 100 mA cm−2 in 1.0 m HClO4 and maintains performance stability and structure integrity under prolonged operation. Moreover, it presents a 3.5-fold increase in precious metal mass activity over Pt/C at η = 80 mV. Theoretical calculations reveal that the electronic interactions generated by Pt-modification of Ru and hydrogenated TiO2 surfaces provide multiple active sites with improved Hads energetics compared to pure Pt and Ru
Molecular mechanisms of the anticancer action of fustin isolated from Cotinus coggygria Scop. in MDA-MB-231 triple-negative breast cancer cell line
No full textThe aim of the present work was to investigate some of the molecular mechanisms and targets of the anticancer action of the bioflavonoid fustin isolated from the heartwood of Cotinus coggygria Scop. in the triple-negative breast cancer cell line MDA-MB-231. For this purpose, we applied fluorescence microscopy analysis to evaluate apoptosis, necrosis, and mitochondrial integrity, wound healing assay to study fustin antimigratory potential and quantitative reverse transcription-polymerase chain reaction to analyze the expression of genes associated with cell cycle control, programmed cell death, metastasis, and epigenetic alterations. A complex network-based bioinformatic analysis was also employed for protein-protein network construction, hub genes identification, and functional enrichment. The results revealed a significant induction of early and late apoptotic and necrotic events, a slight alteration of the mitochondria-related fluorescence, and marked antimotility effect after fustin treatment. Of 34 analyzed genes, seven fustin targets were identified, of which CDKN1A, ATM, and MYC were significantly enriched in pathways such as cell cycle, intrinsic apoptotic signaling pathway in response to DNA damage and generic transcription pathway. Our findings outline some molecular mechanisms of the anticancer action of fustin pointing it out as a potential oncotherapeutic agent and provide directions for future in vivo research
Synthesis, structure, physico-chemical properties and biological activity of copper(II) ketoiminate complexes derived from N-naphthyl- and N-quinolyl-β-aminovinyl ketones
No full textFour novel copper(II) complexes of N-quinolyl or N-naphthyl substituted β-aminovinyl ketones, derivatives of either benzoylacetaldehyde or benzoylacetone were synthesized. Their structures and physico-chemical properties were studied using single-crystal XRD analysis, XANES and EXAFS, IR, EPR, and UV–Vis spectroscopy, magnetic measurements, and DFT calculations. All investigated metal chelates have the ML2 composition. The square-planar coordination geometry in the N-naphthyl substituted copper(II) ketoiminate complexes is formed by bidentate NO coordination of the deprotonated β-aminovinyl ketones. Both copper(II) N-quinolyl substituted ketoiminate complexes have square-pyramidal coordination geometry with one of two deprotonated β-aminovinyl ketone ligands coordinated as NNO tridentate. In the copper(II) complex of N-quinolyl substituted β-aminovinyl ketone derived from benzoylacetaldehyde, the remaining coordination sites are occupied with the enamine and quinoline nitrogen atoms of the second ligand. On the other hand, in the copper(II) complex prepared from its β-methyl derivative the second ligand coordinates through the azomethine nitrogen and the enamine ketone oxygen. Antibacterial, antifungal, and protistocidal activity of compounds was tested. The β-methyl substituted N-quinolyl-β-aminovinyl ketone and its copper(II) complex exhibit the most pronounced biological activity
Ispitivanje aromatičnosti neorganskih kompleksa
No full textAromatičnost je jedan od najvažnijih koncepata u savremenoj hemiji, posebno u organskoj i organometalnoj hemiji. Ovaj pojam opisuje izuzetnu stabilnost molekula koji poseduju cikličnu, ravnu strukturu sa delokalizovanim elektronima, što se često ogleda i kroz specifične magnetne, spektroskopske i strukturne karakteristike. Iako je benzen klasičan primer aromatičnog jedinjenja, danas se pojam aromatičnosti primenjuje i na širok spektar kompleksnih sistema, uključujući i metalne i heterociklične strukture. Međutim, aromatičnost nije direktno merljiva veličina, te se za njeno ispitivanje koristi više teorijskih i računarskih metoda koje procenjuju elektronsku delokalizaciju, magnetne osobine i druge pokazatelje.
U okviru ovog rada ispitivana je aromatičnost niza kompleksa korišćenjem tri metode, metoda mapa magnetno indukovanih struja, metoda hemijskog pomeranja nezavisno od jezgra i metoda energije aromatične stabilizacije. Ispitivani molekuli uključuju derivate pentan-2,4-diona, pentan-2,4-diimina i pentan-2,4-ditiona, kod kojih su metil grupe zamenjene atomima vodonika, čime su dobijeni jednostavniji propanski analozi: propan-1,3-dion, propan-1,3-diimin i propan-1,3-dition. Analizirani su njihovi kompleksi sa metalima, a rezultati su prikazani u Tabeli 1. Cilj ovog istraživanja bio je da se uporede rezultati dobijeni različitim metodama i utvrdi koji pristup daje najpouzdaniju procenu aromatičnosti, kao i da se identifikuje koji kompleksi pokazuju izraženu aromatičnost i u kom stepenu.
Dobijeni rezultati ukazuju na prednosti i ograničenja svake od metoda i daju dublji uvid u prirodu aromatičnosti kod proučavanih sistema. Ovaj rad doprinosi boljem razumevanju različitih tehnika u kvantifikaciji aromatičnosti i može biti koristan u budućim istraživanjima koja se bave ovim fenomenom. Takođe, naglašava značaj izbora odgovarajuće metode za precizno ocenjivanje aromatičnosti u različitim hemijskim sistemima, što može imati široku primenu u razvoju novih jedinjenja sa specifičnim funkcionalnim svojstvima