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Two new nitrato complexes of zinc and nickel with 1,4,8,11-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane (tpmc), have been synthesized and characterized. The IR spectral peaks showed that the coordinated and ionic nitrate ions are in agreement with the formula proposed by elemental analysis. Conductometric titrations predicted methanol to be a convenient solvent for synthesis and revealed the stoichiometry of the complexes, while molar electrical conductivities indicated a 1 : 3 complex electrolyte type for the zinc complex, and a 1 : 2 complex electrolyte type for the nickel complex. The optimized complex structure was obtained by molecular modeling and density functional theory calculations. The biological activity of the novel complexes was examined by screening eight different bacterial strains and two cancer cell lines. The zinc complex showed better antimicrobial activity against the bacterial strains, while the complexes did not show significance antiproliferative activity toward cancer cells MCF-7 and MDA-MB-231.

Here, we report the design of a disposable single-drop voltammetric sensor for the quantitative determination of antipsychotic drug trifluoperazine (TFP). The sensor was built using inkjet-printed carbon nanotube (CNT) electrodes, which were modified with dimercaptosuccinic acid (DMSA)-coated magnetite nanoparticles uniformly dispersed over reduced graphene oxide nanosheets (DMSA/Fe3O4/RGO). The used modifying materials were characterized by electron microscopy techniques (transmission electron microscopy (TEM) and field emission-scanning electron microscopy (FE-SEM)), X-ray powder diffraction, ζ-potential measurements, dynamic light scattering (DLS), and electrochemical methods (cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS)). The developed sensor, best operated at pH 7 in the Britton-Robinson buffer solution (BRBS), shows linear electrocatalytic activity with TFP in the concentration range of 1-50 μM, a low detection limit of 0.54 μM, and excellent selectivity, repeatability, and reproducibility with an relative standard deviation (RSD) of 2.4%. A voltammetric approach using square wave voltammetry (SWV) is a sensitive technique under optimized conditions for the analytical determination of submicromolar amounts of TFP. Bare CNT and RGO- and DMSA/Fe3O4-modified CNT electrodes showed lower electrocatalytic activity than the DMSA/Fe3O4/RGO/CNT electrode. The development of this kind of TFP sensor based on nanoparticle-decorated graphene nanosheets can offer a tool for point-of-care applications as sensors in biomedicine.

Mefenamic acid and indomethacin, medicaments belonging to the group of non-steroidal anti-inflammatory agents, were determined separately and simultaneously at anodically prepared BDDE. Differential pulse voltammetry was used to establish simple and fast analytical procedure based on electrooxidation of mefenamic acid at 0.6 V and indomethacin at 1.0 V (and 1.1 V). At optimal conditions, it was suitable for highly sensitive and selective determination of these compounds with LODs comparable to previously reported modified electrodes. Additionally, considering the importance of these compounds, we proposed precise and accurate quantification of these species based on green and simple pre-treatable electrochemical sensor. The effect of interfering agents (tablet ingredients and vitamins) was appeared to be negligibly confirming a favourable selectivity of the method. The proposed method was analytically applied by simultaneously determining mefenamic acid and indomethacin in pharmaceutical formulations.

The aim of this study was to determine the content of some elements (Pb, Cd, Hg, Fe, Cu, Zn, As) in muscle tissue of Prussian carp (Carassius auratus gibelio) from seven different lakes in the Belgrade region, Serbia. Concentrations of Pb, Hg and As in fish muscle tissues from all examined lakes were under the maximum residual levels prescribed by the European Union (EU) and the maximum allowed concentrations (MAC) for Serbia. In all investigated fish, levels of Cd exceeded maximum allowed concentrations (0.05 mg kg-1). Data on the finding of elements in fish speak concurrently about the safety of fish as food and are good indicators of environmental pollution.

Two new nitrato complexes of zinc and nickel with 1,4,8,11-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane (tpmc), have been synthesized and characterized. The IR spectral peaks showed that the coordinated and ionic nitrate ions are in agreement with the formula proposed by elemental analysis. Conductometric titrations predicted methanol to be a convenient solvent for synthesis and revealed the stoichiometry of the complexes, while molar electrical conductivities indicated a 1 : 3 complex electrolyte type for the zinc complex, and a 1 : 2 complex electrolyte type for the nickel complex. The optimized complex structure was obtained by molecular modeling and density functional theory calculations. The biological activity of the novel complexes was examined by screening eight different bacterial strains and two cancer cell lines. The zinc complex showed better antimicrobial activity against the bacterial strains, while the complexes did not show significance antiproliferative activity toward cancer cells MCF-7 and MDA-MB-231.

In recent years, the search for effective anticancer compounds based on transition metal complexes has been the focus of medical investigations. The synergy between the ruthenium(II) and N-alkylphenothiazine counter-ions (chlorpromazine hydrochloride, thioridazine hydrochloride and trifluoperazine dihydrochloride, respectively) through the formation of three different complexes (1-3) was investigated. We explored whether the selected counter-ions and complexes might affect redox homeostasis and genome integrity of normal human blood cells, and induce an inhibition of Na+/K+-ATPase and AChE at pharmacologically relevant doses. Our results have shown that counter-ions and complexes did not affect the activity of Na+/K+-ATPase, while AChE activity was inhibited in a dose-dependent manner. All investigated compounds disturbed the viability and redox homeostasis of lymphocytes. Complexes 1 and 2 displayed potent cytotoxic and prooxidant action while complex 3 behaved as a weaker genotoxic inducer. Still, the tested complexes appeared to be less genotoxic and more cytostatic than the corresponding counter-ions. The effects of selected complexes were also tested in PC12 and U2OS cancer cells with special attention being given to the ability of phenothiazines to affect dopamine D2 receptors. Using the confocal laser scanning microscopy, we observed that all the complexes reduced cell viability. Although all investigated complexes have been bound to the dopamine receptor D-2-eGFP, only complex 3 reduced its surface density and increased its lateral mobility in investigated cell lines. Albeit the role of alternative targets for complex 3 cannot be ruled out, its effects should be further examined as potential treatment strategy against cancer cells that overexpress D2.

Background. Mycotoxins are toxic secondary metabolites, which are synthesized from a large number of intermediates from the primary metabolism of saprophytic molds. Aflatoxins, due to their genotoxic and carcinogenic effects, are the most important group of mycotoxins from the aspect of their impact on human and animal health. Of all known aflatoxins, AFB1 is the most frequent, with the most harmful impact on human and animal health. Scope and Approach. Due to their prevalence and toxicity, monitoring the presence of aflatoxins in the food chain is required. The scope of this paper is to provide information on the presence of aflatoxins in animal feed and in milk. This paper describes temperature increases in Europe that are contributing to the increased presence of aflatoxins in food, as well as aflatoxin prevention and protection measures. Key Findings and Conclusions. During the last decade, serious contamination of corn with aflatoxins was recorded in southern Europe. In the summer of 2012, Serbia recorded high concentrations of aflatoxins in corn and milk. Based on climate change data, it is expected that aflatoxin contamination in corn will become more frequent., Uvod. Mikotoksini su toksični produkti sekundarnog metabolizma saprofitskih plesni, koji se sintetišu od velikog broja međuprodukata primarnog metabolizma. Aflatoksini zbog genotoksičnog i kancerogenog dejstva predstavljaju najznačajniju grupu mikotoksina sa aspekta uticaja na zdravlje ljudi i životinja. Od svih poznatih aflatoksina, AFB1 je najfrekventniji sa najštetnijim uticajem na zdravlje ljudi i životinja. Cilj i pristup. Zbog svoje zastupljenosti i toksičnosti aflatoksini zahtevaju praćenje njihovog prisustva u lancu hrane. Cilj ovog rada je da pruži informaciju o prisustvu aflatoksina u hrani za životinje i u mleku. U radu su opisane globalne temperaturne promene koje povećavaju prisustvo aflatoksina u hrani, kao i mere prevencije i zaštite Ključni nalazi i zaključak. Tokom poslednje decenije, zabeleženo je ozbiljno zagađenje kukuruza sa aflatoksinima u južnoj Evropi. Republika Srbija je u leto 2012. godine zabeležila visoke koncentracije aflatoksina u kukuruzu i u mleku. Na osnovu podataka o klimatskim promenama, očekuje se da kontaminacije aflatoksinima u kukuruzu postanu učestalije.

Two non-steroidal antiinflammatory drugs indomethacin and mefenamic acid were coordinated to Ru(II)-arenes to afford four new complexes. The cytotoxic activities of the ligands and ruthenium complexes were tested in three human cancer cell lines (K562, A549, MDA-MB-231) and non-tumour human fetal lung fibroblast cells (MRC-5) by MTT assay. Cytotoxicity studies revealed that indomethacin Ru(II)-arene complexes 1 and 3 displayed good cytotoxicity and apparent cytoselective profiles. The IC50 values obtained in leukemia K562 cells were comparable to those of cisplatin (10.3 mu M (CDDP), 11.9 mu M (1) and 13.2 mu M (3)). Flow cytometric analysis of 1 and 3 in triple-negative breast cancer MDA-MB-231 cells revealed an interesting mechanism of action. At IC50 concentrations, 1 and 3 arrested cell cycle progression in S phase and caused rapid accumulation of cells in sub-G1 phase (up to 48%), while Annexin V-FITC/PI staining showed simultaneous occurrence of apoptotic and necrotic cell populations at approximately similar levels of 20%. Measurement of reactive oxygen species (ROS) production by DCFH-DA staining confirmed the potential of 1 and 3 to increase ROS even more than cisplatin. The interaction of the complexes with serum albumins showed their potential ability to bind tightly and reversibly to albumins. The affinity of the complexes to calf-thymus DNA was investigated by UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for competitive studies of the complexes with ethidium bromide, revealing that their interaction probably occurs via intercalation. Taken together, the results strongly suggest the potential of complexes 1 and 3 to alter cell cycle progression and cause DNA-damage by means of direct DNA-binding or indirectly by ROS production.

U ovom radu sintetisano je četiri nova arenska kompleksa Ru(II) sa dva nesteroidna antiimflamatorna leka, indometacin i mefenaminskom kiselininom. Kompleksi su sintetisani polazeći od metanolnog rastvora polaznog Ru(II) polusendvič jedinjenja i baznog metanolnog rastvora odgovarajućeg liganda. Strukture novih kompleksa određene su NMR i IC spektroskopijom, kao i masenom spektrometrijom. Pokazano je da se ligandi koordinuju monodentatno preko karboksilnih kiseonika. Citotoksična aktivnost liganada i kompleksa ispitana je na tri ćelijske linije humanog kancera i zdravih humanih fibroblastnih ćelija, korišćenjem MTT metode. IC50 vrednosti dobijene na ćelijama leukemije K562 bile su uporedive sa onim za cisplatinu (10.3 µM (cisplatina), 11.9 µM (kompleks 1) i 13.2 µM (kompleks 3)). Korišćenjem protočne citometrije pokazano je da ovi kompleksi pri IC50 koncentracijama zaustavljaju ćelijski ciklus u S fazi. Merenje produkcije reaktivnih kiseoničnih DCFH-DA metodom potvrdilo je njihov potencijal da povećavaju ROS više od cisplatine., Two non-steroidal antiinflammatory drugs, indomethacin and mefenamic acid, were coordinated to Ru(II)-arenes to give four new complexes. These four complexes were synthesized by mixing methanolic solution of starting half-sandwich Ru complexes with base solution of ligand in methanol. Structures of complexes were determinated by NMR, IR spectroscopy and mass spectrometry. It was shown that they coordinates monodentatly via carboxylic oxygen. The cytotoxic activity of the ligands and ruthenium complexes was tested in three human cancer cell lines and non-tumour human fetal lung fibroblast cells by MTT assay. The IC50 values obtained in leukemia K562 cells, were comparable to cisplatin (10.3 µM (CDDP), 11.9 µM (1) and 13.2 µM (3)). Flow cytometric analysis of these conplexes, showed that at IC50 concentrations, they arrested cell cycle progression in the S phase. Measurement of reactive oxygen species (ROS) production, by DCFH-DA staining, confirmed their potential to increase ROS even more than cisplatin.

Three new ruthenium(II) complexes 1-3 containing N-alkylphenothiazine molecules were synthesized by reaction of [RuCl2(eta(6)-P-cymene)](2) with chlorpromazine hydrochloride (1), trifluoperazine dihydrochloride (2) or thioridazine hydrochloride (3). The compounds of the general formula L[RuCl3(eta(6)-p-cymene)] were characterized by elemental analysis and spectroscopic methods (FT-IR, UV-Vis, H-1 and C-13 NMR). Complex 2 was structurally characterized by single crystal X-ray diffraction. In vitro cytotoxic activity of complexes 1-3 were assayed in four human carcinoma cell lines MCF-7, MDA-MB-453 (breast carcinoma), SW-480 (colon carcinoma) and IM9 (myeloma multiple cells). The highest cytotoxicity (12.1 lt = IC50 lt = 17.3 mu M) and induced a total (SW-480) or almost total cell death (MCF-7. MDA-MB-453) at 25 mu M in 48 h of treatment were observed for complex 2. The influence of three different doses (0.4, 4.5 and 90.4 mu M/kg bw) of complex 2 on activities of antioxidants enzymes (superoxide dismutase (SOD) and catalase (CAT)) and lactate dehydrogenase (LDH) were investigated under physiological conditions. The effects on nitrite production (NO2-) and level of erythrocytes malondialdehyde (MDA) in rats blood were evaluated, too.

The aim of this study was to determine the influence of different feed composition and cultivation on the composition of fatty acids, their relationships, and the cholesterol content in the tissue of rainbow trout (Oncorhynchus mykiss). Trout were reared in ponds at two different altitudes and raised on different feeds. The total amount of monounsaturated fatty acids in fillets of both groups showed no statistically significant difference. However, higher levels of n-6 fatty acids were found in Pond I trout fillets than in Pond II fillets, while Pond II fillets contained almost even amounts of n-3 and n-6 fatty acids. Total cholesterol content in Pond I trout fillets was significantly lower (p<0.05) than in Pond II fillets. The results indicate that the final composition of the trout fillets was mostly dependent on the feed the live fish had consumed; the altitude of the ponds had less effect. Also, both groups of trout could be used in the human diet as biologically valuable foods. Practical application: Our results show influence of altitude, feed, and fatty acid composition of feed on trout fillets. The average fatty acid level in the trout fillets increased in the order SFA

The aim of this study was to investigate the presence of heavy metals/metalloids (Pb, Cd, Hg, Cu, Fe, Zn, As) in the muscle tissue of fish from the Danube River (two locations: Zemun and Grocka). For the purpose of heavy metal determination in fish muscle, 120 samples of six different fish species, Prussian carp, barbel, bream, carp, pike perch, and catfish were collected. For determining heavy metals, we used microwave oven digestion and atomic absorption spectrometer methods. The highest average content of Pb (0.084 +/- 0.004 mg kg(-1)), Cd (0.082 +/- 0.003 mg kg(-1)), Hg (0.466 +/- 0.006 mg kg(-1)), and As (0.333 +/- 0.007 mg kg(-1)) was found in the muscle of carp (an omnivorous fish) from Grocka, while the highest average level of Fe (13.60 +/- 0.03 mg kg(-1)) was deposited in bream (also omnivorous) from Zemun. Also, the average Cu level (1.62 +/- 0.13 mg kg(-1)) was the highest in catfish muscle (a carnivorous fish) from Grocka, while the highest Zn content (11.16 +/- 0.17 mg kg(-1)) was determined in muscle of Prussian carp (an omnivorous fish) from Zemun. The highest content of heavy metals (Cu, Fe, and Zn, respectively) in muscle of the six different types of fish from both locations was symmetrically arranged by species (catfish, barbel, and Prussian carp, respectively). Concentrations of Pb, Hg, and As in the Danube River fish muscle were under the maximum residual levels prescribed by the European Union (EU) and the maximum allowed concentrations (MAC) for Serbia. On the other hand, in all fish muscle from both locations (Zemun and Grocka), higher concentrations of Cd than prescribed (MAC) were found, with the exception of bream and pike perch.

A simple and fast method for determination of two phenothiazine drugs, chlorpromazine (CPZ) and thioridazine (TDZ), at the boron-doped diamond electrode (BDDE) was proposed. Oxidation peaks on potentials higher than 1 V were used for quantitation of investigated phenothiazines due to better selectivity over common interfering compounds in urine. Differential pulse voltammetry was applied for trace determination of CPZ and TDZ, in Britton-Robinson buffer solution at optimal pH. Under optimized DPV conditions a linear analytical curve was obtained from 1.0x10(-7) to 4.0x10(-5) M with a detection limit of 0.3x10(-7) M (for CPZ) and in the concentration range of 2x10(-7) M to 4.0x10(-5) M, with a detection limit of 1.2x10(-7)M (for TDZ). The applicability of the method was proved by determination of CPZ and TDZ by proposed procedures in spiked urine samples. The electrochemical behavior of those two important tranquilizers in different solvents was described, exploring the possibility of simultaneous determination.

A simple and fast method for determination of two phenothiazine drugs, chlorpromazine (CPZ) and thioridazine (TDZ), at the boron-doped diamond electrode (BDDE) was proposed. Oxidation peaks on potentials higher than 1 V were used for quantitation of investigated phenothiazines due to better selectivity over common interfering compounds in urine. Differential pulse voltammetry was applied for trace determination of CPZ and TDZ, in Britton-Robinson buffer solution at optimal pH. Under optimized DPV conditions a linear analytical curve was obtained from 1.0x10(-7) to 4.0x10(-5) M with a detection limit of 0.3x10(-7) M (for CPZ) and in the concentration range of 2x10(-7) M to 4.0x10(-5) M, with a detection limit of 1.2x10(-7)M (for TDZ). The applicability of the method was proved by determination of CPZ and TDZ by proposed procedures in spiked urine samples. The electrochemical behavior of those two important tranquilizers in different solvents was described, exploring the possibility of simultaneous determination.

The aim of this study was the investigation of water, sediments and fish tissues contamination with heavy metals. All samples were taken from the Danube River in Belgrade region, a location upstream from Batajnica. Concentrations of Cd, Hg and Pb in water samples were not detected, while concentrations of Zn, Fe, Cu and As were in the range of 0.004 - 0.330 mg L-1. Iron was the most deposited metal in sediment samples in contrast to water samples where all investigated metals were detected. For the purpose of heavy metals determination in fresh fish tissue, fifteen samples of three different fish species, silver carp (Hypophthalmichthys molitrix), common carp (Cyprinus carpio) and wels catfish (Silurus glanis) were collected. Concentrations of Pb, Cd, As and Hg were determined in the digestive tract, liver and muscle by absorption spectroscopy. The highest concentration of Pb was in the digestive tract in all three fish species, ranging from 0.036 to 1.518 μg g-1, while Cd was mostly deposited in the liver. Concentrations of As were in the range of 0.36 - 0.73 μg g-1 in Hypophthalmichthys molitrix, 0.013 - 0.18 μg g-1 in Cyprinus carpio and 0.003 - 0.005 μg g-1 in Silurus glanis tissues, while the content of Hg was equal in all tested tissues of carp. Concentrations of all metals were found to be present in the fish samples at different levels, but these values are under the maximum residual levels prescribed by the European Union (EU) and the maximum allowed concentrations (MAC) for Serbia, so the fish meat is acceptable for the human consumption., Cilj ovog rada je ispitivanje kontaminacije teškim metalima vode, sedimenta kao i tri različite vrste sveže ribe. Svi uzorci su uzeti iz Dunava u regionu Beograda, tačnije uzvodno od Batajnice. Koncentracije Cd, Hg i Pb u uzorcima vode su približne graničnim vrednostima detekcije, dok su koncentracije Zn, Fe, Cu i As u opsegu 0.004 - 0.330 mg L-1. Gvožđe je najprisutniji metal u uzorcima sedimenata za razliku od uzoraka vode gde su svi ispitivani metali podjednako zastupljeni. U cilju ispitivanja teških metala u tkivima riba sakupljeno je po petnaest uzoraka tri različite vrste riba, tolstolobika (Hypophthalmichthys molitrix), šarana (Cyprinus carpio) i soma (Silurus glanis). Koncentracije Pb, Cd, As i Hg određene su u digestivnom traktu, jetri i mišićnom tkivu sveže dunavske ribe metodom absorpcione spektroskopije. Najveća koncentracija Pb zabeležena je u digestivnom traktu kod svih ispitivanih vrsta riba i to u opsegu 0.036 - 1.518 μg g-1, dok je Cd uglavnom deponovan u jetri. Koncentracija As bila je u opsegu 0.36 - 0.73 μg g-1 u tkivu Hypophthalmichthys molitrix, 0.013 - 0.18 μg g-1 u tkivu Cyprinus carpio i 0.003 - 0.005 μg g-1 u tkivu Silurus glanis, dok je sadržaj Hg bio izjednačen u svim ispitivanim tkivima šarana. Koncentracije svih metala u tkivima riba su različite i ispod maksimalno dozvoljenih koncentracija predvidjenih pravilnikom Evropske Unije i maksimalno dozvoljenih koncentracije (MDK) u Srbiji, a riba može da se koristi za ishranu ljudi.