Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand.

Platinum-based drugs are widely recognized efficient anti-tumor agents, but faced with multiple undesirable effects. Here, four dinuclear platinum(II) complexes, [{Pt(1,2-pn)Cl}2(µ-pydz)]Cl2 (C1), [{Pt(ibn)Cl}2(µ-pydz)]Cl2 (C2), [{Pt(1,3-pn)Cl}2(µ-pydz)]Cl2 (C3) and [{Pt(1,3-pnd)Cl}2(µ-pydz)]Cl2 (C4), were designed (pydz is pyridazine, 1,2-pn is ( ±)-1,2-propylenediamine, ibn is 1,2-diamino-2-methylpropane, 1,3-pn is 1,3-propylenediamine, and 1,3-pnd is 1,3-pentanediamine). Interactions and binding ability of C1-C4 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV-Vis, fluorescence emission spectroscopy and molecular docking. Binding affinities of C1-C4 complexes to the bovine serum albumin (BSA) has been monitored by fluorescence emission spectroscopy. The tested complexes exhibit variable cytotoxicity toward different mouse and human tumor cell lines. C2 shows the most potent cytotoxicity, especially against mouse (4T1) and human (MDA-MD468) breast cancer cells in the dose- and time-dependent manner. C2 induces 4T1 and MDA-MD468 cells apoptosis, further documented by the accumulation of cells at sub-G1 phase of cell cycle and increase of executive caspase 3 and caspase 9 levels in 4T1 cells. C2 exhibits anti-proliferative effect through the reduction of cyclin D3 and cyclin E expression and elevation of inhibitor p27 level. Also, C2 downregulates c-Myc and phosphorylated AKT, oncogenes involved in the control of tumor cell proliferation and death. In order to measure the amount of platinum(II) complexes taken up by the cells, the cellular platinum content were quantified. However, C2 failed to inhibit mouse breast cancer growth in vivo. Chemical modifications of tested platinum(II) complexes might be a valuable approach for the improvement of their anti-tumor activity, especially effects in vivo.

Degradation of tartrazine by Oxone® in the presence of cobalt based catalyst supported on pillared montmorillonite - Efficient technology even in extreme conditions.

The catalytic degradation of hazardous organic contaminants in industrial wastewater is a promising technology. Reactions of tartrazine, the synthetic yellow azo dye, with Oxone® in the presence of catalyst in strong acidic condition (pH 2), were detected by using UV-Vis spectroscopy. In order to extend the applicability profile of Co-supported Al-pillared montmorillonite catalyst an investigation of Oxone® induced reactions were performed in extreme acidic environment. The products of the reactions were identified by liquid chromatography-mass spectrometry (LC-MS). Along with the catalytic decomposition of tartrazine induced by radical attack (confirmed as unique reaction path under neutral and alkaline conditions), the formation of tartrazine derivatives by reaction of nucleophilic addition was also detected. The presence of derivatives under acidic conditions slowed down the hydrolysis of tartrazine diazo bond in comparison to the reactions in neutral environment. Nevertheless, the reaction in acidic conditions (pH 2) is faster than the one conducted in alkaline conditions (pH 11). Theoretical calculations were used to complete and clarify the mechanisms of tartrazine derivatization and degradation, as well as to predict the UV-Vis spectra of compounds which could serve as predictors of certain reaction phases. ECOSAR program, used to estimate toxicological profile of compounds to aquatic animals, indicated an increase in the harmfulness of the compounds identified by LC-MS as degradation products from the reaction conducted for 240min. It could be concluded that an intensification of the process parameters (higher concentration of Oxone®, higher catalyst loading, increased reaction time, etc.) is needed in order to obtain only biodegradable products.

Heracleum orphanidis: chemical characterisation, and comparative evaluation of antioxidant and antimicrobial activities with specific interest in the influence on Pseudomonas aeruginosa PAO1.

GC-FID and GC-MS were used to determine the chemical composition of the essential oil of the aerial parts of Heracleum orphanidis Boiss. Also, the HPLC-DAD/ESI-ToF-MS profile of the methanol extracts of aerial parts and roots was determined. The main components of the essential oil were n-octanol, octyl hexanoate and n-octyl acetate, while coumarins were the most prevalent compounds in methanol extracts. An evaluation of antioxidant activity showed that the methanol and aqueous extracts of the aerial parts had the highest potential. In terms of antimicrobial activity determined by microdilution assays, the essential oil and methanol extract of the roots showed the greatest effectiveness. The colonies of Pseudomonas aeruginosa PAO1 treated with H. orphanidis samples produced less toxic pyocyanin, showed lower twitching and flagella mobility and biofilm formatting was reduced. The analyses in this study showed the considerable biological potential of H. orphanidis considering free radicals and various pathogenic strains, including the wild type of P. aeruginosa.

Chemistry of the sternal gland secretion of the Mediterranean centipede Himantarium gabrielis (Linnaeus, 1767) (Chilopoda: Geophilomorpha: Himantariidae).

The geophilomorph centipede, Himantarium gabrielis, when disturbed, discharges a viscous and proteinaceous secretion from the sternal glands. This exudate was found by gas chromatography-mass spectrometry, liquid chromatography-high resolution mass spectrometry, liquid chromatography-mass spectrometry-mass spectrometry and NMR analyses to be composed of hydrogen cyanide, benzaldehyde, benzoyl nitrile, benzyl nitrile, mandelonitrile, mandelonitrile benzoate, 3,7,6O-trimethylguanine (himantarine), farnesyl 2,3-dihydrofarnesoate and farnesyl farnesoate. This is the first report on the presence of benzyl nitrile and mandelonitrile benzoate in secreted substances from centipedes. Farnesyl 2,3-dihydrofarnesoate is a new compound, while himantarine and farnesyl farnesoate were not known as natural products. A post-secretion release of hydrogen cyanide by reaction of mandelonitrile and benzoyl nitrile was observed by NMR, and hydrogen cyanide signals were completely assigned. In addition, a protein component of the secretion was analysed by electrophoresis which revealed the presence of a major 55 kDa protein. Analyses of the defensive exudates of other geophilomorph families should produce further chemical surprises.

Chemical composition, cytotoxic and antioxidative activities of ethanolic extracts of propolis on HCT-116 cell line.

BACKGROUND: Propolis is a complex resinous sticky substance that honeybees collect from buds and exudates of various plants. Owing to its versatile biological and pharmacological activities, propolis is widely used in medicines, cosmetics and foods. The aim of this study was to evaluate the cytotoxic and antioxidative effects of various ethanolic extracts of propolis (EEPs) on human colon cancer cell line HCT-116 and compare them with their composition determined by HPLC-DAD. RESULTS: The most abundant flavonoids in all samples were chrysin, pinocembrin and galangin (12.697-40.811 µg mg⁻¹), while the main phenolic acids were caffeic acid, ferulic acid and isoferulic acid. Dose- and time-dependent inhibition of growth of HCT-116 cells was observed for all propolis samples, with IC50 values ranging from 26.33 to 143.09 µg mL⁻¹. Differences in cytotoxic activity of propolis samples were associated with differences in their composition. All EEP samples reduced both superoxide anion radical and nitrite levels and also had strong DPPH-scavenging activity. CONCLUSION: All tested propolis samples had pronounced cytotoxic and antioxidative activities.

Defensive secretions in Callipodella fasciata (Latzel, 1882; Diplopoda, Callipodida, Schizopetalidae).

The small millipede Callipodella fasciata secretes an earthy smell when disturbed. This secretion was obtained by CH(2) Cl(2) extraction from specimens of both sexes and was identified by GC/MS analyses to be composed of p-cresol (96.5%), phenol (3.5%), and p-ethylphenol (traces). This is the first identification of these compounds in an epigean European callipodidan species and the first report of intergeneric differences in the chemical composition of defensive secretions in callipodidans. These compounds have repellent, antimicrobial, and antifungal properties.

Defensive secretions in three species of polydesmids (Diplopoda, Polydesmida, Polydesmidae).

Nine compounds were detected in three different millipede species: Polydesmus complanatus (L.), Brachydesmus (Stylobrachydesmus) avalae Curcic & Makarov, and Brachydesmus (Stylobrachydesmus) dadayi Verhoeff. Benzaldehyde, benzyl alcohol, benzoylnitrile, benzyl methyl ketone, benzoic acid, benzyl ethyl ketone, mandelonitrile, and mandelonitrile benzoate were identified by GC-FID and GC-MS analyses. Hydrogen cyanide was detected qualitatively by the picric acid test. Benzyl ethyl ketone, benzyl methyl ketone, and benzyl alcohol were detected for the first time in polydesmidan millipedes. Benzoylnitrile was the major component in all three hexane extracts. These compounds are suspected to be active in the defensive secretions of these millipede species.

Identification of secretory compounds from the European callipodidan species Apfelbeckia insculpta.

Defensive secretions of the callipodidan species Apfelbeckia insculpta contain a p-cresol as the main component and phenol in traces. This is the first identification of these compounds in a European callipodidan species. The repugnatory glands of A. insculpta are of the spirobolid type and consist of a spherical reservoir, a simple duct, and a valvular cuticular infolding that opens onto the lateral surface of the millipede via a pore.