Aleksandar Savić

Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity

Data on medical applications of cerium oxide nanoparticles CeO2 (CONP) are promising, yet information regarding their action in cells is incomplete and there are conflicting reports about in vitro toxicity. Herein, we have studied cytotoxic effect of CONP in several cancer and normal cell lines and their potential to change intracellular redox status. The IC50 was achieved only in two of eight tested cell lines, melanoma 518A2 and colorectal adenocarcinoma HT-29. Self-propagating room temperature method was applied to produce CONP with an average crystalline size of 4 nm. The results confirmed presence of Ce(3+) and O(2-) vacancies. The induction of cell death by CONP and the production of reactive oxygen species (ROS) were analyzed by flow-cytometry. Free radicals related antioxidant capacity of the cells was studied by the reduction of stable free radical TEMPONE using electron spin resonance spectroscopy. CONP showed low or moderate cytotoxicity in cancer cell lines: adenocarcinoma DLD1 and multi-drug resistant DLD1-TxR, non-small cell lung carcinoma NCI-H460 and multi-drug resistant NCI-H460/R, while normal cell lines (keratinocytes HaCaT, lung fetal fibroblasts MRC-5) were insensitive. The most sensitive were 518A2 melanoma and HT-29 colorectal adenocarcinoma cell lines, with the IC50 values being between 100 and 200 μM. Decreased rate of TEMPONE reduction and increased production of certain ROS species (peroxynitrite and hydrogen peroxide anion) indicates that free radical metabolism, thus redox status was changed, and antioxidant capacity damaged in the CONP treated 518A2 and HT-29 cells. In conclusion, changes in intracellular redox status induced by CONP are partly attributed to the prooxidant activity of the nanoparticles. Further, ROS induced cell damages might eventually lead to the cell death. However, low inhibitory potential of CONP in the other human cell lines tested indicates that CONP may be safe for human usage in industry and medicine.

Satureja horvatii essential oil: In vitro antimicrobial and antiradical properties and in situ control of Listeria monocytogenes in pork meat

The dominant compounds in Satureja horvatii oil were p-cymene (33.14%), thymol (26.11%) and thymol methyl ether (15.08%). The minimum inhibitory concentration (MIC) varied from 0.03 to 0.57 mg/mL for bacteria, and from 0.56 to 2.23 mg/mL for yeast strains, while minimum bactericidal/yeast-cidal concentration (MBC/MYC) varied from 0.07 to 1.15 mg/mL and 1.11 to 5.57 mg/mL for bacteria and yeasts, respectively. The antiradical potential of the essential oil was evaluated using hydroxyl radical (•OH) generated in Fenton reaction. The meat preserving potential of essential oil from Satureja horvatii was investigated against L. monocytogenes. Essential oil successfully inhibited development of L. monocytogenes in pork meat. Sensorial evaluation on flavor and color of meat was performed. The color and flavor of meat treated with essential oil improved after 4 days of storage. S. horvatii essential oil can act as a potent inhibitor of food spoiling microorganisms, in meat products and also can be a useful source of natural antioxidants.

New and Highly Potent Antitumor Natural Products from Marine-Derived Fungi: Covering the Period from 2003 to 2012

This review covers the 2003-2012 literature data published for antitumor natural products from marine-derived fungi. The focus is on new and highly potent cytotoxic compounds, together with details related to the relevant fungal species. It describes 22 promising bioactives, originating mainly from symbiotic fungi. The chemical structures of all highlighted organic molecules are briefly discussed.

Further in vitro evaluation of antiradical and antimicrobial activities of phytol

The antiradical activity of phytol was evaluated by electron paramagnetic resonance towards hydroxyl radical (√OH), superoxide anion radical (), methoxy radical (√CH2OH), carbon-dioxide anion radical (), as well as towards nitric-oxide radical (√NO) and 2,2-diphenyl-1-picrylhydrazyl (√DPPH) radical. It reduced the production of all tested radicals showing more promising activity against , √CH2OH and √DPPH radicals (56%, 50% and 48%, respectively) in comparison with √NO, and √OH radicals (38%, 23% and 15%, respectively). The antimicrobial activity of phytol was evaluated by the microdilution method against eight bacterial and eight fungal strains. To varying degrees, it was proven to be active against all tested bacteria and fungi (MIC 0.003–0.038 mg/mL and MBC 0.013–0.052 mg/mL, MIC 0.008–0.016 mg/mL and MFC 0.090–0.520 mg/mL, respectively). According to the obtained results, medical foods containing phytol may support development of new therapies for heart disease.

Synthesis and in vitro Anticancer Activity of Ruthenium–Cymene Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N′-diacetate-Type Ligands

Herein we describe the synthesis, characterization, and anticancer activity of novel p‐cymeneruthenium(II) complexes containing methyl, ethyl, n‐propyl, and n‐butyl esters of (S,S)‐ethylenediamine‐N,N′‐di‐2‐(3‐cyclohexyl)propanoic acid. The results of IR, UV/Vis, ESIMS, 1H, and 13C NMR characterization reveal that ligand coordination occurs through nitrogen donor atoms of the ester ligands, with the organoruthenium moiety being kept in complex. These ruthenium(II) complexes are cytotoxic toward various cancer cell lines including leukemic HL‐60, K562, and REH cells (IC50: 1.0–20.2 μM), with the n‐butyl ester complex being the most effective. It causes apoptotic cell death associated with mitochondrial depolarization, caspase activation, phosphatidylserine exposure, and DNA fragmentation. Importantly, the n‐butyl ester complex is more effective against leukemic patients′ blood mononuclear cells relative to those from healthy control subjects, thus indicating a fairly selective antileukemic action of RuII‐based compounds.

Fingerprint detection and using intercalated CdSe nanoparticles on non-porous surfaces

A fluorescent nanocomposite based on the inclusion of CdSe quantum dots in porous phosphate heterostructures, functionalized with amino groups (PPH-NH2@CdSe), was synthesized, characterized and used for fingerprint detection. The main scopes of this work were first to develop a friendly chemical powder for detecting latent fingerprints, especially in non-porous surfaces; their further intercalation in PPH structure enables not to spread the fluorescent nanoparticles, for that reason very good fluorescent images can be obtained. The fingerprints, obtained on different non-porous surfaces such as iron tweezers, mobile telephone screen and magnetic band of a credit card, treated with this powder emit a pale orange luminescence under ultraviolet excitation. A further image processing consists of contrast enhancement that allows obtaining positive matches according to the information supplied from a police database, and showed to be more effective than that obtained with the non-processed images. Experimental results illustrate the effectiveness of proposed methods.

Structural Differences Between Lignin Model Polymers Synthesized from Various Monomers

In a plant cell wall, lignin is synthesized from several monomeric precursors, combined in various ratios. The variation in monomer type and quantity enables multifunctional role of lignin in plants. Thus, it is important to know how different combinations of lignin monomers impact variability of bond types and local structural changes in the polymer. Lignin model polymers are a good model system for studies of relation between variations of the starting monomers and structural variations within the polymer. We synthesized lignin model polymers from three monomers, CF—based on coniferyl alcohol and ferulic acid in monomer proportions 5:1 and 10:1 (w/w), CP—based on coniferyl alcohol and p-coumaric acid in proportion 10:1 (w/w) and CA—based on pure coniferyl alcohol. We studied structural modifications in the obtained polymers, by combining fluorescence microscopy and spectroscopy, FT-IR and Raman spectroscopy, in parallel with determination of polymers’ molecular mass distribution. The differences in the low Mw region of the distribution curves of the 10:1 polymers in comparison with the CA polymer may be connected with the increased content of C=C bonds and decreased content of condensed structures, as observed in FT-IR spectra and indicated by the analysis of fluorescence spectra. The 5:1 CF polymer contains a different type of structure in comparison with the 10:1 CF polymers, reflected in its simpler Mw distribution, higher homogeneity of the fluorescence emitting structures and in the appearance of a new high-wavelength emission component. We propose that this component may originate from π-conjugated chains, which are longer in this polymer. The results are a contribution to the understanding of the involvement of structural variations of lignin polymers in the cell wall structural plasticity.

The relationship of physicochemical properties to the antioxidative activity of free amino acids in Fenton system.

Herein we compared antioxidative activities (AA) of 25 free L-amino acids (FAA) against Fenton system-mediated hydroxyl radical (HO(•)) production in aqueous solution, and examined the relation between AA and a set of physicochemical properties. The rank order according to AA was: Trp > norleucine > Phe, Leu > Ile > His >3,4-dihydroxyphenylalanine, Arg > Val > Lys, Tyr, Pro > hydroxyproline > α-aminobutyric acid > Gln, Thr, Ser > Glu, Ala, Gly, Asn, Asp. Sulfur-containing FAA generated different secondary reactive products, which were discriminated by the means of electron paramagnetic resonance spin-trapping spectroscopy. AA showed a general positive correlation with hydrophobicity. However, when taken separately, uncharged FAA exhibited strong positive correlation of AA with hydrophobicity whereas charged FAA showed negative or no significant correlation depending on the scale applied. A general strong negative correlation was found between AA and polarity. Steric parameters and hydration numbers correlated positively with AA of nonpolar side-chain FAA. In addition, a decrease of temperature which promotes hydrophobic hydration resulted in increased AA. This implies that HO(•)-provoked oxidation of FAA is strongly affected by hydrophobic hydration. Our findings are important for the understanding of oxidation processes in natural and waste waters.

Two metaheuristic approaches for solving multidimensional two-way number partitioning problem

In this paper, we address two metaheuristic approaches, a Variable Neighborhood Search (VNS) and an Electromagnetism-like metaheuristic (EM), on an NP-hard optimization problem: Multi-dimensional Two-way Number Partitioning Problem (MDTWNPP). MDTWNPP is a generalization of a Two-way Number Partitioning Problem (TWNPP), where a set of vectors is partitioned rather than a set of numbers. The simple k-swap neighborhoods allow an effective shaking procedure in the VNS search. The attraction-repulsion mechanism of EM is extended with a scaling procedure, which additionally moves EM points closer to local optima. Both VNS and EM use the same local search procedure based on 1-swap improvements. Computational results were obtained on 210 standard instances. Direct comparison with results from the literature confirm the significance of applying these methods to MDTWNPP.

Novel and highly potent antitumour natural products from cnidarians of marine origin

This article covers the 2003–2012 literature published for marine natural products from the phylum Cnidaria. The focus is on new and highly potent antitumour substances, together with details related to the organism sourced. It describes 12 promising bioactives isolated from 7 species.