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Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors with 1-benzhydryl piperazine as a surface recognition group that differ in hydrocarbon linker. Surprisingly, in vitro HDAC screening identified two selective HDAC6 inhibitors (6b, IC50 = 186 nM and 9b, IC50 = 31 nM), as well as two non-selective nanomolar HDAC inhibitors (7b and 8b). The influence of linker chemistry of synthesized inhibitors on HDAC6 potency was studied using structure-based molecular modelling. The breast cancer cell-lines (MDA-MB-231 and MCF-7) were used to evaluate compound mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities, leading to 8b as the most promising compound. In our study, 8b is identified as the HDAC inhibitor with very potent anti-angiogenic, anti-metastatic and anti-tumor effects in zebrafish MDA-MB-231 xenograft models at low micromolar concentrations.

Uvođenjem putarine određeni broj vozaca napusta koriscenje autoputeva i prelazi na alternativnu mrežu dvotracnih puteva. Naime, određeni broj korisnika izbegava puteve sa naknadom zbog „dodatnih troskova“ putarine. Prema tome, ovaj rad je usmeren ka ispitivanju stavova korisnika po pitanju izbegavanja koriscenja puteva sa naplatom putarine na teritoriji Republike Srbije. Cilj rada je da se da odgovor na pitanje koji su kljucni razlozi za njihovo izbegavanje. Istraživanje je sprovedeno na mreži alternativnih dvotracnih puteva, na lokacijama visoke atraktivnosti, u neposrednoj blizini autoputa. Rezultati sprovedenog istraživanja omogucavaju sagledavanje problema izbegavanja naplate putarine iz perspektive korisnika, sto pruža jasniju sliku upravljacu autoputeva prilikom sagledavanja i resavanja ovog problema.

Selective histone deacetylase 6 (HDAC6) inhibition is promoted as a rational strategy to develop safer anticancer drugs compared to nonselective HDAC inhibitors. Nevertheless, considerably more nonselective HDAC inhibitors have been undergoing clinical trials. Initially, we focused on synthesizing a selective HDAC6 inhibitor, with 1-benzhydryl piperazine as surface recognition CAP group, and its nonselective analogues with small structural perturbations in the hydrocarbon linker. Surprisingly, the in vitro HDAC screening identified two selective HDAC6 inhibitors (BDR-6, IC50=186 nM and BDR-9, IC50=31 nM), along with two nonselective nanomolar HDAC inhibitors (BDR-7 and BDR-8). Insight into the structural determinants for selective HDAC6 inhibition was studied by molecular dynamics. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate their in vitro anticancer, antiimigratory and anti-invasive activities, highlighting BDR-8 as the most promising lead compound. Toxicity assessment using zebrafish embryos indicated BDR-9 as a teratogenic, cardiotoxic and hepatotoxic compound, whereas the BDR-8 inhibitor at the same concentration (50 μM) was proven to be nontoxic. Finally, BDR-8 represents a promising and safe HDAC inhibitor with very potent antiangiogenic, antimetastatic and antitumor effects in the zebrafish MDA-MB-231 xenograft model in low micromolar concentrations.

A photochemically promoted intramolecular cyclization of aryl-, vinyl-, and alkyliodo allenes has been developed. The optimal conditions employed [Ir(ppy)2(dtbbpy)]PF6 (1 mol%) as catalyst affording products with high exo selectivity in moderate to good yields. Chiral substrates showed diastereoselectivity of up to 95/5 favoring trans product.

Pyrrole derivatives with C(2)-aryl substituents are an important and widespread class of heterocyclic compounds. Their synthesis can be accomplished using several strategic variants which usually entail either protection of the N–H functionality followed by the arylation, or a direct arylation. Although direct arylation is a preferable process due to a reduced number of synthetic steps, it often requires vigorous conditions or challenging reagents. To this synthetic repertoire, we add a novel method that is based on the dual role of the arylating agent. It serves as the nitrogen protecting group while also being involved in the arylation step. Deprotection as a final stage is carried out simultaneously utilising amines as reacting components. This approach ensures relatively mild conditions and exclusive C(2) selectivity yielding 2-arylpyrroles with the amide functionality. While aromatic amines are not suitable partners under studied conditions, most likely due to lower nucleophilicity, aliphatic amines, either primary or secondary, afford products in good yields.

Disruption of the redox balance in the body causes oxidative stress that can initiate many diseases. While antioxidants reduce the level of oxidizing compounds in the medium, prooxidants promote the opposite process and were used in therapies in particular those of cancer diseases. In this study, a series of azolyl lactones, were tested in human serum as a biological matrix and the obtained values of their oxy scores (OS) were compared. The antioxidative properties of these compounds were also tested under conditions of induced oxidative stress using an external prooxidant, t-butylhydroperoxide. The results showed that the sulphur analogue 4-azolyl coumarin 5 has the best antioxidant properties (OS -2.2), while the halogenated derivatives of pyrazolylcoumarin 7 and 8 act as prooxidant, but successfully resist oxidative stress (OS 2.7 and 2.0). Related phthalides and isocoumarins showed prooxidative properties, but azolyl isocoumarins 10 and 11 show the strongest resistance to oxidative stress, reflected in their negative oxy score value (OS -2.1 and OS -1.1). The results demonstrated that combining two pharmacophores with known redox properties can produce potent compounds in both directions, with the antioxidative and the prooxidative characteristics.

Methanol extracts of mosaic puffball (Handkea utriformis, Bovistella utriformis, Lycoperdon utriforme, Calvatia utriformis - current name is a subject of debate), from three different stages - mycelium (HUMIC), immature (HUI) and mature fruiting bodies (HUM) were characterized and tested for antioxidant, antimicrobial and inhibitory activity on tyrosinase, acetyholinesterase (AChE), butyrylcholinesterase (BuChE) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA-R). Immature, edible, fruiting bodies were shown to be a good source of antioxidants (11.5 mg/g of extract) and cholesterol-lowering agent, lovastatin (234 mu g/g of extract), and exhibited significant antimicrobial activity. In addition, HUI showed good and selective AChE (4.48 mg/mL) and non-lovastatin related HMG-CoA-R inhibition (1.16 mg/mL), which all together suggests that regular consumption of it may have health benefits. Mature fruiting bodies, inedible due to powdery consistence, have been used in traditional medicine for wound treatment; their extract was relatively rich in free ergosterol (31.65 mg/g of extract), N-acetylglucosamine (24 mg/g of extract), alpha-tocopherol (4 mg/g of extract) and had best overall antioxidant activity, which was in correlation with its highest phenolic content (19.4 mg GAE/mL). It also exhibited significant tyrosinase inhibitory activity (0.22 mg/mL) and thus could be used in medicinal and cosmetic products for wound healing and bleaching. Mycelium, which can be easily grown in laboratory conditions did not have the same properties as, neither immature or mature fruiting bodies, although it showed prominent antimicrobial activity, notably against Pseudomonas aeruginosa (MIC = 0.0625 mg/mL) and could be a source of antimicrobial compounds. &nbsp

Several coumarin derivatives with a directly attached azole substituent at C‐4 were synthesized and biologically studied for their anticancer properties. The cell lines used for this investigation (HeLa, K‐562, MDA‐MB‐53, and MCF‐7) demonstrated different sensitivities. The best response in the MTT (3‐(4,5‐dimethyl‐2‐thiazolyl)‐ 2,5‐diphenyl‐2H‐tetrazolium bromide) assay was shown by K‐562 cells, with compounds displaying activity (3c, IC50 3.06 μM; 4a, IC50 5.24 μM; 4c, IC50 4.7 μM) similar to that of cisplatin (IC50 ~6 μM), which was used as the standard. The studied azole‐substituted coumarins demonstrated weaker activity toward other cell lines, except for compound 4c, which was equally potent in the case of MCF‐7 cells. Additional biological evaluations supported interference with the cell cycle as a potential mechanism of action and confirmed the absence of toxicity in zebrafish embryos. On the basis of these initial results, 4‐azole coumarins should be explored further. Although their activity would need additional optimization, the fact that these compounds are fragment‐like structures with MW

We describe herein the synthesis and laccase mediated oxidation of six novel 1,4-dihydropyridine (DHP)-based hexahydroquinolines (DHP1-DHP3) and decahydroacridines (DHP4-DHP6). We employed different laccase enzymes with varying redox potential to convert DHP1-DHP3 and DHP4-DHP6 to the corresponding pyridine-containing tetrahydroquinoline and octahydroacridine derivatives, respectively. Intensively coloured products were detected in all biocatalytic reactions using laccase from Trametes versicolor (TvLacc), possibly due to the presence of conjugated chromophores formed in products after oxidation. The NMR assessment confirmed that the oxidation product of DHP1 was its corresponding pyridine-bearing tetrahydroquinoline derivative. Laccase from Bacillus subtillis (BacillusLacc) was the most efficient enzyme for this group of substrates using HPLC assessment. Overall, it could be concluded that DHP2 and DHP5, bearing catecholic structures, were easily oxidized by all tested laccases, while DHP3 and DHP6 containing electron-withdrawing nitro-groups are not readily oxidized by laccases. DHP4 with decahydroacridine moiety consisting of three condensed six-membered rings that contribute not only to the volume but also to the higher redox potential of the substrate rendered this compound not to be biotransformed with any of the mentioned enzymes. Overall, we showed that multiple analytical approaches are needed in order to assess biocatalytical reactions. Supplementary material: [https://cherry.chem.bg.ac.rs/handle/123456789/4568]

The quantitative structure-retention relationship (QSRR) models are not only employed in retention behaviour prediction, but also in an in-depth understanding of complex chromatographic systems. The goal of the present research is to enable the comprehensive understanding of retention underlying the separation in β-cyclodextrin (CD) modified reversed-phase high performance liquid chromatography (RP-HPLC) systems, through the development of mixed QSRR models. Moreover, the amount of β-CD adsorbed on the stationary phase surface (β-CDA) is added as the model's input in order to evaluate its contribution to both model performances and retention. Nuclear magnetic resonance (NMR) experiments were conducted to confirm the predicted inclusion complex structures and support the application of in silico tools. The most significant descriptors revealed that retention is governed by the steric factors 7.5 A distant from the geometrical centre of a molecule, 3D arrangement of atoms determining the molecular size and shape, lipophilicity indicated by topological distances, as well as the unbound system's energy, related to the inclusion complex formation. In addition, a notable effect of the pH of the aqueous phase on the retention of ionizable analytes was shown. In the case of pH of the aqueous phase and β-CDA the change in retention behaviour of the studied analytes was observed only at the highest β-CDA value (5.17 μM/m2), but it was not related to the ionization state of analytes. When the analytes did not change the ionization form across the investigated studied pH range, and the acetonitrile content in the mobile phase was 25% (v/v), the retention factor had low values regardless of the β-CDA; under these circumstances the retention is probably acetonitrile driven.

Octahydro-dipyrroloquinoline skeleton is the building component of a very few naturally occurring compounds. Nevertheless, these natural products have been attractive synthetic targets, and their study commanded development of efficient synthesis of this core. While the reported methods are based on the dimerization procedure of N-arylpyrrolidines of N-arylhomopropargyl amines, our approach relay on dipolar cycloaddition/amination sequence. This strategic approach allows sequential introduction of aromatic moieties increasing the product diversity and hence may be useful in further exploration of incargranine B or seneciobipyrrolidine derivatives.

U procesu planiranja, projektovanja i definisanja argumenata neophodnih za donosenje odluka o ulaganju investicija u predložena resenja puta ili mreže, znacajno mesto zauzimaju i faze vrednovanja projektnih resenja. Pod pojmom vrednovanje podrazumeva se definisanje argumenata na osnovu kojih se donose odluke od kojih zavisi hoce li, kada, gde i koja od planiranih resenja prerasti u realnost, ili ce ostati neostvarene ideje. Za efikasno izvrsavanje proracuna ukupnih koristi, u analitickim postupcima, znacajnu ulogu imaju merodavni parametri saobracajnog toka, a pre svega PGDS i merodavni saobracajni protoci. Međutim, problem se javlja u slucaju pogresnog koriscenja merodavnih protoka u fazama projektovanja i vrednovanja. Uputstva preporucuju i obavezuju analiticare da merodavne protoke analiziraju po klasama, sto je veoma retko rađeno u dosadasnjoj praksi. Iz tog razloga, u ovom radu je sprovedena generalna analiza merodavnih saobracajnih protoka na mreži puteva u Republici Srbiji za period od 2011. do 2015. godine. Poseban akcenat je stavljen na karakter saobracajnih tokova, vremenske neravnomernosti, distribuciju protoka po klasama i analizu eksploatacionih brzina u zavisnosti od merodavnih protoka i klasa casovnih protoka. Rezultati ovog rada bi trebalo da omoguce sprovođenje argumentovanijih analiza u fazama projektovanja, saobracajnom i ekonomskom vrednovanju putnih projekata.

A facile synthetic route has been developed for the preparation of pyrrolizinone derivatives employing N-allyl imides as starting materials. The nucleophilic addition of a vinyl Grignard reagent/RCM/elimination sequence afforded pyrrolizinones in good yields and has been applied for the preparation of naturally occurring quinolactacide and marinamide.

Recently, growing interest is devoted to investigation of bioactive secondary metabolites of endophytic fungi. Thus, as an extension to our previous achievements related to antimicrobial potential of endophytic fungi, Phomopsis species isolated from conifer needles was selected as appropriately promising natural source for drug discovery. Its dichloromethane and ethanol extracts considerably inhibited growth of Escherichia coli and Staphylococcus aureus. Moreover, the indi-vidual compounds of dichloromethane extract have been separated, collected and purified using semi preparative liquid chromatographic analysis and comprehensively characterized using mass spectrometry (MS) and nuclear magnetic res-onance spectroscopy (NMR). Based on their antimicrobial activity and unique structural characteristics in comparison with well-established drugs from the same therapeutic category, two dominant compounds (Z)-(Z)-2-acetoxyprop-1-en-1-yl-3-(3-((E)-3,4-dihydroxypent-1-en-1-yl)oxiran-2-yl)acrylate (denoted as 325-3) and (Z)-(Z)-2-acetoxyprop-1-en-1-yl 3-(3-((E)-4-hydroxy-3-oxopent-1-en-1-yl)oxiran-2-yl)acrylate (denoted as 325-5) were recognized as valuable leading structures for future discovery of novel antibiotics.

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Anti-Candida bioassay guided optimization of the culture medium was used in order to enhance the antifungal activity of the soil isolate MS1. Its morphological, physiological and biochemical characteristics, as well as 16S rDNA sequencing, assigned an MS1 isolate to genus Streptomyces. Optimization of the culture medium was achieved by experimental factorial design and response surface methodology. Maximal antifungal components production was obtained with starch, soybean meal and phosphates content of 40.52, 5.10 and 2.21 g/L, respectively. Chromatography and 1H and 13CNMR spectroscopy were employed for purification and structural characterization of antifungal antibiotics concurrently produced by this strain. These antibiotics were identified as polyether carboxylic antibiotic nigericin and guanidyl-polyol macrolide, niphimycin.

Structural variations of the heterocyclic ring of the recently introduced pyrrolidine derived thiourea organocatalysts have been studied. The results showed that the stereoselectivity is highly dependent on the substitution pattern reaching a moderate level, while the yields were generally less influenced by the structural changes. The outlined results may be helpful in further exploration of the thiourea catalyst represented by structure II.

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Telomerase is RNA directed polymerase which acts as reverse transcriptase based on its own RNA component. It is considered to be involved in the pathology of many diseases and is recognized as a potential biomarker. The aims were to determine the sample storage conditions and the time frame for samples analysis, then to prove reliability of enzyme activity measurement with real-time telomeric repeat amplification protocol (TRAP) and to evaluate the suitable standard samples for telomerase activity measurements. Samples used for stability and freeze-thaw study were peripheral blood leukocytes, obtained from apparently healthy persons, patients with diagnosed cancer and cell lines. Telomerase activity was measured using TRAP method, while standard evaluation was done using nuclear magnetic resonance (NMR) technique. Storage at -20 degrees C preserved telomerase activity in samples from cancer patients for at least 14 days (21.46 +/- 0.135 versus 21.84 +/- 0.357, p = .756), while samples obtained from healthy persons should be stored at -80 degrees C. We observed significant decrease of telomerase activity at freeze thaw cycle 5 in cancer patients' samples (21.46 +/- 0.135 versus 23.09 +/- 0.316, p lt .05), and in healthy persons' ones already at cycle 3 (22.74 +/- 0.107 versus 24.85 +/- 0.151, p lt .05). Telomerase activity from cell lines samples showed overall greater stability regarding the storage period and freeze-thaw cycles and it was considered for standard sample, which was confirmed by NMR analysis. Telomerase enzyme had adequate stability while efficacy, linearity, and reproducibility of TRAP method were acceptable for bio-analytical methods. All this indicated that telomerase could be a reliable biomarker.

The separation and characterization of the unknown degradation product of second-generation antipsychotic drug ziprasidone are essential for defining the genotoxic potential of the compound. The aim of this study was to develop a simple UHPLC method coupled with tandem mass spectrometry (MS/MS) for chemical characterization of an unknown degradant, and the separation and quantification of ziprasidone and its five main impurities (I-V) in the raw material and pharmaceuticals. Chromatographic conditions were optimized by experimental design. The MS/MS fragmentation conditions were optimized individually for each compound in order to obtain both specific fragments and high signal intensity. A rapid and sensitive UHPLC-MS/MS method was developed. All seven analytes were eluted within the 7 min run time. The best separation was obtained on the Acquity UPLC BEH C-18 (50 x 2.1 mm x 1.7 mu m) column in gradient mode with ammonium-formate buffer (10 mm; pH 4.7) and acetonitrile as mobile phase, with the flow rate of 0.3 mL min(-1) and at the column temperature of 30 degrees C. The new UHPLC-MS/MS method was fully validated and all validation parameters were confirmed. The fragmentation pathways and chemical characterization of an unknown degradant were proposed and it was confirmed that there are no structural alerts concerning genotoxicity.

A novel thiourea organocatalyst was rationally designed by altering a typical H-bonding pattern of thiourea derivatives and utilising the potential of the 3,5-bis(trifluoromethyl) phenyl motif to participate in the H-bond formation. This unique catalyst afforded the products of the alpha-amination and Michael reaction in excellent yields and with a high level of stereoselectivity. Although additional studies are necessary to establish the full potential of the catalyst and to broaden its application further, the presented results may indicate alternative routes for further exploration of the thiourea class of organocatalysts.

Four sesquiterpene lactones (SLs), including three undescribed proline-SL conjugates, the guaianolides calophyllamine A and 8-epiixerisamine A, and the eudesmanolide calophyllamine B, were isolated from the methanol extract of Hieracium calophyllum R. Uechtr. (Compositae) flowering heads. Another known guaianolide, crepiside E, was detected in Hieracium L. species for the first time. Their structures were elucidated using extensive 1D and 2D NMR spectroscopy in combination with HRMS. The isolated SLs were used as external standards for qualitative and quantitative LC-MS analysis of the dry methanol extracts of the flowering aerial parts of 28 Hieracium species from the Balkan Peninsula. Guaianolides were the dominant SLs in 27 species studied. The chemosystematic significance of detected SLs was evaluated using multivariate statistics (PCA, nMDS and UPGMA). Differentiation between the main groups was well supported. All four compounds significantly and equally contributed to the differences between the species. In addition, the eudesmanolide calophyllamine B could be a significant chemosystematic marker for H. sect. Villosa (Griseb.) Gremli s.l. and Glauciformia (Freyn) Zahn–Italica (Fr.) Av. Touv.

A series of 23 novel anthraquinone-chalcone hybrids containing amide function was synthesized and structurally characterized. Sixteen compounds exerted strong cytotoxic activities against K562, Jurkat and HL-60 leukemia cell lines and significantly lower cytotoxic effects against normal MRC-5 cells, indicating very high selectivity in their anticancer action. The compounds 6g, 6u and 6v activate apoptosis in K562 cells through the extrinsic and intrinsic apoptotic pathway. The compound 6e triggered apoptosis in K562 cells only through the extrinsic apoptotic pathway. Treatment of K562 cells with each of these four compounds caused decrease in the expression levels of MMP2, MMP9, and VEGF, suggesting their anti-invasive, antimetastatic and antiangiogenic properties. The compounds 6g and 6v downregulated expression levels of miR-155 in K562 cells, while compounds 6e and 6u upregulated miR-155 levels in treated cells, in comparison with control cells. The structure-based 3-D QSAR models for 6f, 6e, 6i and 6l describe pro-apoptotic activity against caspase-3. © 2018 Elsevier Ltd

A one-pot, domino process was developed as an alternative approach for the preparation of 2-unsubstituted imidazolones. The methodology utilizes readily accessible bisamides, which upon a dehydration/cyclisation sequence produced imidazolones in good yields. The transformation relies on the compatibility of the dehydrating agent and base, and the reaction conditions tolerate various functional groups.

Herein, we report the synthesis and structural characteristics of three tetrazole-containing compounds, 1-benzyl-1H-tetrazole (bntz), 1-benzyl-1H-tetrazol-5-amine (bntza) and 1-(4-methoxybenzyl)-1H-tetrazol-5-amine (mbntza) and the corresponding silver(I) complexes of the general formula [Ag(NO3-O)(L-N4)(2)](n), L = bntz (1), bntza (2) and mbntza (3). Silver(I) complexes 1-3 and 1-benzyl-1H-tetrazoles have been studied in detail by NMR, IR and UV-Vis spectroscopic methods and the structures of 1 and 2 have been determined by single-crystal X-ray diffraction analysis. The results of these analyses revealed a monodentate coordination of the ligands to Ag(I) ion via the N4 tetrazole nitrogen. The antimicrobial potential of silver(I) complexes 1-3 was evaluated against the broad panel of Gram-positive and Gram-negative bacteria and fungi, displaying their remarkable inhibiting activity with MIC (minimal inhibitory concentration) values in the range 2-8 and 0.16-1.25 mu g/mL (3.8-16.3 and 0.31-2.15 mu M), respectively. On the other hand, 1-benzyl-1H-tetrazoles used for the synthesis of the silver(I) complexes were not active against the investigated strains, suggesting that the activity of the complexes originates from the Ag(I) ion exclusively. Moreover, silver(I) complexes 1-3 have good therapeutic potential, which can be deduced from their moderate cytotoxicity on the human fibroblast cell line MRC5, with IC50 values falling in the range 30-60 mu g/mL (57.7-103.4 mu M). (C) 2018 Elsevier Ltd. All rights reserved. This is peer-reviewed version of the following article: Andrejević, T. P.; Nikolić, A. M.; Glišić, B. Đ.; Wadepohl, H.; Vojnovic, S.; Zlatović, M.; Petković, M.; Nikodinovic-Runic, J.; Opsenica, I. M.; Djuran, M. I. Synthesis, Structural Characterization and Antimicrobial Activity of Silver(I) Complexes with 1-Benzyl-1H-Tetrazoles. Polyhedron 2018, 154, 325–333. [https://doi.org/10.1016/j.poly.2018.08.001] Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/2992]

In this paper, we have presented the results of our investigation of galvanoluminescence (GL) originating from oxide films obtained by anodization of titanium in alkaline solutions. For the first time we have measured weak GL during the anodization of titanium and found strong influence of sample's surface pretreatment, as well as anodizing conditions (current density and electrolyte temperature). GL is more intense for rougher titanium samples, higher current density, and higher temperature of electrolyte. Spectral characterization of GL showed that there are wide GL bands present mostly in the visible and near infrared spectral region. As the potential of anodization approaches the breakdown voltage, a numerous transient sparks appear superimposed on the GL. Keywords: Titanium, Anodization, Galvanoluminescence, Breakdown

The renewable silver-amalgam film electrode (Hg(Ag)FE) was applied for voltammetric characterization and determination of semi-synthetic macrolide antibiotics azithromycin (AZI), clarithromycin (CLA) and roxithromycin (ROX) in the Britton-Robinson buffer as supporting electrolyte ranging the pH from 4.0 to 11.9. All three macrolides showed reduction signals in fairly negative potential range. During direct cathodic square wave voltammetric (SWV) investigations conducted over the potential range from −0.75 V to −2.00 V vs SCE, either one or two reduction peaks were obtained in the potential range from −1.5 to −1.9 V. The shapes and intensities of the signals depend on the applied pH values in wider pH ranges. For analytical purposes concerning the development of direct cathodic SWV and adsorptive stripping SWV (SW-AdSV) methods the neutral and slightly alkaline media were suitable as pH 7.2, pH 7.4 and pH 7.0 for AZI, CLA and ROX, respectively. Based on the cyclic voltammograms recorded at these pH values, adsorption-controlled electrode kinetics process can be proposed for all three macrolides. Furthermore, the water suppressed 1 H NMR measurements in the pH range between 6.0 and 10.5 indicated that the macrolide molecules at the optimal analytical conditions are predominantly in protonated form via their tertiary amino groups which supported in all three cases their adsorption on the appropriately polarized Hg(Ag)FE electrode. The optimized direct cathodic SWV methods showed good linearity in concentration ranges 4.81–23.3 μg mL −1 , 1.96–28.6 μg mL −1 and 1.48–25.9 μg mL −1 for AZI, CLA and ROX, respectively. The development of the SW-AdSV methods resulted in the linear responses at lower concentration ranges as 1.0–2.46 μg mL −1 , 0.05–0.99 μg mL −1 and 0.10–0.99 μg mL −1 , for AZI, CLA and ROX, respectively. The relative standard deviation for all developed methods was not higher than 1.0% except the SWV method for AZI with 4.7%. In the case of all three investigated macrolide antibiotics the protonated form of the tertiary amino group(s) at appropriate accumulation potential and time favored the adsorption of the ionic form of the target molecules offering the opportunity for the development of SW-AdSV methods for their trace level analysis on Hg(Ag)FE. Optimized SW-AdSV method was applied for determination of ROX in pharmaceutical preparation Runac ® .

Pd-catalysed arylation–acetoxylation cascade, a previously reported methodology, was applied in the functionalisation of unsymmetrical dienes. Both explored classes of compounds, isoquinoline and β-carboline-derived dienes, afforded single regioisomers. Although further improvements of the process are necessary, primarily due to lower yields, the described functionalisation of the studied compounds might be useful in the synthesis of emetine and related naturally occurring compounds. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 172009]

Stereoselectivity, achieved in the title Michael reaction, is found to be highly dependent on the substitution pattern of the pyrrolidine derived organocatalyst employed.

A novel thiourea organocatalyst was rationally designed by altering a typical H-bonding pattern of thiourea derivatives and utilising the potential of the 3,5-bis(trifluoromethyl)phenyl motif to participate in the H-bond formation. This unique catalyst afforded the products of the α-amination and Michael reaction in excellent yields and with a high level of stereoselectivity. Although additional studies are necessary to establish the full potential of the catalyst and to broaden its application further, the presented results may indicate alternative routes for further exploration of the thiourea class of organocatalysts.

Allenamides derived from amino acids participate in the cascade transformations catalyzed by Pd0 allowing consecutive formation of two five-membered rings. The developed methodology provides an access to annulated indoles which can be transformed to functionalized indoxyl derivatives, retaining a structural motif embedded in several natural products.

In this paper, we have investigated photocatalytic properties of TiO 2 /WO 3 coatings formed by plasma electrolytic oxidation (PEO) of titanium in 12-tungstosilicic acid water solution and compared with photocatalytic activity of pure TiO 2 coatings. The photocatalytic activity of the coatings is evaluated by measuring the degradation of methyl orange under simulated sunlight conditions. Photocatalytic activity of TiO 2 /WO 3 coatings varied with duration of PEO process and higher photoactivity is obtained for a shorter process time. Photocatalytic activity of TiO 2 /WO 3 coatings is related to morphology and phase and elemental composition of coatings. The oxide coatings morphology is strongly dependent on PEO time. The elemental components of the coatings are Ti, W and O. The oxide coatings are partly crystallized and mainly composed of WO 3 and anatase. Decrease in the number of microdischarge channels and agglomeration of particles on the surface leads to a decrease in photocatalytic activity. The reduction of the photocatalytic activity with increased time of PEO process is accompanied with the increase of WO 3 concentration on the coatings’ surface. Diffuse reflectance spectroscopy has shown that coatings enriched with tungsten oxide exhibit significant red shift with respect to the pure TiO 2 coatings. TiO 2 /WO 3 coatings with improved catalytic activity, compared to pure TiO 2 coatings, are grouped around energy band gap of 2.6 eV. The results of PL measurements of TiO 2 /WO 3 coatings are in agreement with photocatalytic activities. The increase of PL intensity corresponds to decrease of photocatalytic activity of the coatings, indicating fast recombination of electron–hole pairs.

A Gram-positive, red-pigment-producing bacterial strain, designated JS520 was isolated from the pristine sediment from the cave on mountain Miroc in Serbia. Strain was confirmed to belong to Streptomyces genus based on phenotypic and genetic analysis. Streptomyces sp. JS520 has the ability to produce exceptionally high amounts of deep red pigment into both solid and liquid media. Liquid chromatography and mass spectroscopy of the purified pigments revealed the major component to be undecylprodigiosin (93 %) with minor component being oxidatively cyclized derivative. The pigment production was affected by medium composition, temperature, pH, and the aeration rate. By medium optimization, yields of undecylprodigiosin of 138 mg l(-1) were achieved, what is the highest level of undecylprodigiosin production reported for the members of Gram-positive Streptomyces genus. Purified pigment had antimicrobial properties against bacterial Bacillus and Micrococcus species (50 mu g ml(-1)) and against Candida albicans species (100-200 mu g ml(-1) range). The ability to affect auto-oxidation of the linoleic acid was demonstrated for the purified undecylprodigiosin, suggesting antioxidative properties of this pigment. Multiple ecophysiological roles of the pigment were revealed by comparing cultures grown under pigment-producing and pigment-nonproducing conditions. Cells grown under undecylprodigiosin-producing conditions could tolerate presence of hydrogen peroxide exhibiting three times smaller zones of inhibition at 100 mM H2O2. Undecylprodigiosin-producing cells were also less susceptible to tetracycline, kanamycin, chloramphenicol, and 8-hydroxyquinoline. While the growth of the cells not producing pigment was completely inhibited by 15 min of exposure to ultraviolet light (254 nm), cells producing undecylprodigiosin and cells supplied with purified pigment in vitro showed survival rates at 22 and 8 %, respectively.

Two broad luminescence peaks with clearly pronounced structure, extending from roughly 18,200 to 18,800 cm−1 and from 19,000 to 19,700 cm−1 with the maxima at approximately 18,500 and 19,500 cm−1, respectively, are obtained during plasma electrolytic oxidation of aluminum. They are assigned to the v′–v″ = −1 and −2 band sequences of the B2Σ+–X2Σ+ emission transition of AlO. The measured intensity distributions are employed to estimate the population of vibrational levels of the upper electronic state, and consequently the mean plasma temperature. The composition of plasma containing aluminum and oxygen under assumption of thermodynamic equilibrium is calculated in the temperature up to 11,000 K in order to explain the appearance of the observed spectral features.

Oxide coatings were formed on tantalum by plasma electrolytic oxidation (PEO) process in 12-tungstosilicic acid. The PEO process can be divided into three stages with respect to change of the voltage–time response. The contribution of electron current density in total current density during anodization results in the transformation of the slope of voltage–time curve. The surface morphology, chemical and phase composition of oxide coatings were investigated by AFM, SEM-EDX, XRD and Raman spectroscopy. Oxide coating morphology is strongly dependent of PEO time. The elemental components of PEO coatings are Ta, O, Si and W. The oxide coatings are partly crystallized and mainly composed of WO 3 , Ta 2 O 5 and SiO 2 . Raman spectroscopy showed that the outer layer of oxide coatings formed during the PEO process is silicate tungsten bronze.

A base promoted cyclization of the protected N-propargylaminopyridines was shown to be an efficient method for the preparation of imidazo[1,2-a] pyridine derivatives. The reactions were carried out with a small excess of base, at room temperature or slightly above producing the heterocyclic products in moderate to good yields. The stereoelectronic properties of substituents on the pyridine ring were shown to influence the cyclization process.

Histone deacetylase 6 (HDAC6) is unique hydrolase within HDAC family, having pleiotropic deacetylase activity against alpha-tubulin, cortactin and dynein. Comprehensively, HDAC6 controls cell motility, apoptosis and protein folding, whereas alterations in its structure and function are related to the pathogenesis of cancer, neurodegeneration and inflammation. To define structural motifs which guide HDAC6 selectivity, we developed and compared three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) models for HDAC1 and HDAC6 inhibitors. The reduction of the bias in conformer generation was supported by virtual docking study by using crystal structures of human HDAC1 and HDAC6 isoforms. Following these findings, the combined ligand-based and fragment-based drug design methodologies were used in the design of selective HDAC6 inhibitors. Group of the most promising novel ligands was selected based on the predicted HDAC6 selectivity, pharmacokinetic profile, synthetic tractability, and in silico cytotoxicity against the wide range of human cancer cell lines.

In this paper, we have investigated luminescence properties of oxide films formed by anodization of aluminum in 12-tungstophosphoric acid. For the first time we have measured weak luminescence during anodization of aluminum in this electrolyte (so-called galvanoluminescence GL) and showed that there are wide GL bands in the visible region of the spectrum and observed two dominant spectral peaks. The first one is at about 425 nm, and the second one shifts with anodization voltage. As the anodization voltage approaches the breakdown voltage, a large number of sparks appear superimposed on the anodic GL. Several intensive band peaks were observed under breakdown caused by electron transitions in W, P, Al, O, H atoms. Furthermore, photoluminescence (PL) of anodic oxide films and anodic-spark formed oxide coatings were performed. In both cases wide PL bands in the range from 320 nm to 600 nm were observed.

A short, efficient, and high-yielding synthesis of 4-aryl-2-aminopyridine derivatives has been developed. The route employs two palladium-catalyzed processes, the Suzuki reaction and the Buchwald–Hartwig amination, as the key steps. The same approach has been used for preparation of the corresponding quinoline derivatives. In addition, a brief study of biological properties showed the anticancer potential of these compounds.

Photoluminescent and optical properties of porous oxide films formed by two-step aluminum anodization at a constant potential of 30 V in sulfamic acid have been investigated after their annealing, ranging from room temperature up to 600 °C. X-ray diffraction reveals the amorphous nature of porous oxide films. Infrared and energy dispersive spectroscopy indicates the presence of sulfuric species incorporated in oxide films during the anodization. Photoluminescence (PL) measurements show PL bands in the range from 320 to 600 nm. There are two peaks in emission and excitation spectra. One emission peak is at constant wavelength centered at 460 nm and the other shifts from 390 to 475 nm, depending on excitation wavelength. For excitation spectra, one spectral peak is at constant wavelength at 270 nm and the other also shifts to longer wavelengths while increasing emission wavelength. Upon annealing of the as-prepared oxide films PL increases reaching maximum value at about 300 °C and then decreases. The results indicate the existence of two PL centers, one placed at surface of the pore wall, while the other positioned inside the oxide films.