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Two newly described oleanane-type saponins (1-2), named tchihatchewosides A-B, along with thirteen known compounds, were isolated from the aerial parts of Cephalaria tchihatchewii using several type of chromatography processes. The structures of all compounds (1-15) were determined by spectroscopic (1D-and 2D-NMR, HR-ESI/ MS) and chemical methods. The cytotoxic activities on CCD 34Lu, A549, CRL5807, CRL 5826, HTB-177 and HeLa cell lines of newly described compounds 1-2 and 1a-2a were evaluated by MTT method using doxorubicin as positive control. Immunomodulatory activity was performed with PMA plus ionomycin in stimulated whole blood cells treated with saponins. The supernatant was analyzed for IL-4, IFN-gamma and IL18 cytokines by ELISA. DMSO was considered as the negative control. The results showed that the only compound 1a was exhibited moderate cytotoxicity against CRL 5826 and CCD 34Lu cells. The compounds 1-2 and prosapogenins 1a-2a stimulated IL18 cytokine release, indicating that they might potentially stimulate the innate immune response., Ege University Scientific Research Projects Coordination Unit [FDK-2019-20292], This study was supported by Ege University Scientific Research Projects Coordination Unit (Project Number: FDK-2019-20292). The authors are grateful to Prof. Dr. H. Sumbul and Prof. Dr. R. S. Gokturk for the collection and identification of the plant. We thank TUBITAK National Metrology Institute for running 600 MHz NMR spectra and HRESI/MS spectra, Ege University Science and Technology Centre for running 400 MHz NMR spectra. And finally, we thank Ege University, Central Research Test and Analysis Laboratory Application and Research Center for GC-MS analysis.

Although it is frequently hypothesized that surface (like surface charge) and physical characteristics (like particle size) play important roles in cellular interactions of nanoparticles (NPs), a systematic study probing this issue is missing. Hence, a comparative cytotoxicity study, quantifying nine different cellular endpoints, was performed with a broad series of monodisperse, well characterized silicon (Si) and germanium (Ge) NPs with various surface functionalizations. Human colonic adenocarcinoma Caco-2 and rat alveolar macrophage NR8383 cells were used to clarify the toxicity of this series of NPs. The surface coatings on the NPs appeared to dominate the cytotoxicity: the cationic NPs exhibited cytotoxicity, whereas the carboxylic acid-terminated and hydrophilic PEG- or dextran-terminated NPs did not. Within the cationic Si NPs, smaller Si NPs were more toxic than bigger ones. Manganese-doped (1% Mn) Si NPs did not show any added toxicity, which favors their further development for bioimaging. Iron-doped (1% Fe) Si NPs showed some added toxicity, which may be due to the leaching of Fe(3+) ions from the core. A silica coating seemed to impart toxicity, in line with the reported toxicity of silica. Intracellular mitochondria seem to be the target for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such an imbalance led to a series of other cellular events for cationic NPs, like decreased mitochondrial membrane potential (ΔΨm) and ATP production, induction of ROS generation, increased cytoplasmic Ca(2+) content, production of TNF-α and enhanced caspase-3 activity. Taken together, the results explain the toxicity of Si NPs/Ge NPs largely by their surface characteristics, provide insight into the mode of action underlying the observed cytotoxicity, and give directions on synthesizing biocompatible Si and Ge NPs, as this is crucial for bioimaging and other applications in for example the field of medicine.

The influence of replacing the d-phenylalanine residue with substituted and unsubstituted azoles on the structure and biological activity of the antibiotic gramicidinS was investigated against a representative panel of Gram-positive and Gram-negative bacteria strains. Substituted triazole derivatives, obtained using a convergent synthetic strategy, are as active as gramicidinS, provided that any substituent on the triazole moiety is not too large. The unsubstituted triazole derivative was biologically less active than the parent natural product, gramicidinS. In general for the triazole series, the hemolytic activity could be correlated with the antibacterial activity, that is, the higher the antibacterial activity, the higher the toxicity towards blood cells. Interestingly, its imidazole counterpart showed high antibacterial activity, combined with significantly diminished hemolytic activity. Turning circles! A series of substituted and unsusbstituted azole derivatives of gramicidinS were synthesised, analysed and tested against a range of bacteria and against erythrocytes. The compound where R=H and X=N exhibited high antibacterial and lower hemolytic activities, while a considerable loss of antibacterial activity was observed for the triazole derivative (R=H; X=CH). © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.