The present study describes the synthesis and anticancer activity of novel octahedral Pt(IV) complexes with cyclohexyl functionalized ethylenediamine-N,N'-diacetate-type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s-cis is the preferred geometry of these Pt(IV) complexes with tetradentate-coordinated (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell-cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt(IV) complexes against various cancer cell lines (IC(50) range: 1.9-8.7 microM) was higher than that of cisplatin (IC(50) range: 10.9-67.0 microM) and proceeded through completely different mechanisms. Cisplatin induced caspase-dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt(IV) complexes caused rapid, caspase-independent, oxidative stress-mediated non-apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.

Ficin forms with different casein specificities are present in different proportions during fruit ripening, which is of importance for applications in the dairy industry. The protection mechanism against insects and fungi, which relies on chitinolytic activity, is the most important in the early phases of flowering and is replaced with other strategies over time.

The light-protected reaction of [(eta(6)-p-cymene)Ru(II)Cl(2)](2) with 1-(2-hydroxyethyl)piperazine in dry methanol, followed by addition of excess NH(4)PF(6), afforded the complex [(eta(6)-p-cymene)Ru(II)(NH(3))(2)Cl](PF(6)) () in 47% yield. Attempts to use the same protocol for the synthesis of [(eta(6)-p-cymene)Os(II)(NH(3))(2)Cl](PF(6)) led to the isolation of the binuclear triply methoxido-bridged arene-osmium compound [{(eta(6)-p-cymene)Os}(2)(mu-OCH(3))(3)](PF(6)) (). Both compounds were characterised by X-ray crystallography and (1)H NMR spectroscopy, and the ruthenium complex also by spectroscopic techniques (IR and UV-vis spectroscopies). The antiproliferative activity of complex in vitro was studied in A549 (non-small cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma) cells and compared to that of [(eta(6)-p-cymene)Ru(II)(en)Cl](PF(6)) (). In contrast to the latter compound, is only modestly cytotoxic in all three cell lines (IC(50): 293-542 muM), probably due to the instability of the diammine ruthenium complex in aqueous solution.

Changes in the structure and fragmentation of land plots, arising from the process of privatization and restitution, as well as from the realization of large-scale infrastructural projects in Southeast Europe and similar, actualize problems in terms of intensive agricultural production, and aesthetic and functional spacing design. The need for initiating new projects regarding land consolidation cycles is increasing with the aim to solve spatial, environmental, and strategic issues in agriculture, as well as to provide appropriate conditions for the application of modern land treating methods. However, land consolidation projects are very complex, long-lasting and financially very demanding. To minimize risk and exclude the possibility of inadequate selection methods, this paper describes the methodology for integrated assessment, which allows decision making on the basis of two or more methods. Per integrated assessment methodology, this study includes several multi-criteria analysis methods, which do not exclude the possibility of integrating other methods. The results obtained in this study are not only beneficial to the South-Eastern Europe region, but also to all countries where land redistribution is expanding.

Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone- and guanidine-containing molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bis-guanylhydrazones were between 2 and 15.6 μg/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitro DNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activation of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent.

Решавање проблема избора катастарске општине за уређење пољопривредног земљишта комасацијом представља задатак који се ставља пред сваку јединицу локалне самоуправе у којој се планира пројектовање и реализација комасационих пројеката. Примена метода вишекритеријумског одлучивања омогућава и олакшава доносиоцима одлука, правилно и коректно доношење одлука. Вишекритеријумска анализа, пре свега, омогућава доношење одлуке у конфликтним условима, када постоји више алтернатива и критеријума, од којих неке треба максимизирати, а неке минимизирати. У раду је обрађена проблематика рангирања катастарских општина за уређење пољопривредног земљишта комасацијом применом TOPSIS методе и презентована евалуација дефинисаног модела у општини Пећинци.

The Municipality of Velika Plana has been taking serious steps when it comes to initiating land consolidation projects which help realize the land reclamation projects in the simplest way. Whit the aim of obtaining the base for carrying out land reclamation projects, this work deals with and presents the survey of the hydrographic features of Municipality of Velika Plana, as well as, water regime and the river basin of the Velika Morava River. Based on measuring data obtained at Ljubicevski most, water gauge survey station we have performed and presented the analysis of the distinctive annual flow over a longer period of time as well as the analysis related to the changes in parameters which occur on an annual basis. On the basis of performed analysis we have been able to determine the amounts of water for irrigation available in the Velika Morava River basin at the territory of Velika Plana, which was the main focus and objective of this research.

Prodigiosins (prodiginines) are a class of bacterial secondary metabolites with remarkable biological activities and color. In this study, optimized production, purification, and characterization of prodigiosin (PG) from easily accessible Serratia marcescens ATCC 27117 strain has been achieved to levels of 14 mg/L of culture within 24 h. Furthermore, environmentally friendly bromination of produced PG was used to afford both novel mono- and dibrominated derivatives of PG. PG and its Br derivatives showed anticancer potential with IC50 values range 0.62–17.00 µg/mL for all tested cancer cell lines and induction of apoptosis but low selectivity against healthy cell lines. All compounds did not affect Caenorhabditiselegans at concentrations up to 50 µg/mL. However, an improved toxicity profile of Br derivatives in comparison to parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 µg/mL applied at 6 h post fertilization caused death rate of 100%, 30% and 0% by PG, PG-Br, and PG-Br2, respectively, which is a significant finding for further structural optimizations of bacterial prodigiosins. The drug-likeness of PG and its Br derivatives was examined, and the novel Br derivatives obey the Lipinski’s “rule of five”, with an exemption of being more lipophilic than PG, which still makes them good targets for further structural optimization.