Novel benzyl-substituted N-heterocyclic carbene-silver acetate complexes: synthesis, cytotoxicity and antibacterial studies

From the reaction of 1-methylimidazole (1a), 4,5-dichloro-1H-imidazole (1b(I)) and 1-methylbenzimidazole (1c) with p-cyanobenzyl bromide (2a), non-symmetrically substituted N-heterocyclic carbene (NHC) [(3a-c)] precursors, 5,6-dimethyl-1H-benzimidazole (1d) and 4,5-diphenyl-1H-imidazole (1e) with p-cyanobenzyl bromide (2a) and benzyl bromide (2b), symmetrically substituted N-heterocyclic carbene (NHC) [(3d-f)] precursors were synthesised. These NHC-precursors were then reacted with silver(i) acetate to yield the NHC-silver complexes (1-methyl-3-(4-cyanobenzyl)imidazole-2-ylidene)silver(i)acetate (4a), (4,5-dichloro-1-(4-cyanobenzyl)-3-methyl)imidazole-2-ylidene)silver(i)acetate (4b), (1-methyl-3-(4-cyanobenzyl)benzimidazole-2-ylidene)silver(i)acetate (4c), (1,3-bis(4-cyanobenzyl)5,6-dimethylbenzimidazole-2-ylidene) silver(i) acetate (4d), (1,3-dibenzyl-5,6-dimethylbenzimidazole-2-ylidene) silver(i) acetate (4e) and (1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene) silver(i) acetate (4f) respectively. Three NHC-precursors 3c-e and four NHC-silver complexes 4b and 4d-f were characterised by single crystal X-ray diffraction. Preliminary in vitro antibacterial activity of the NHC-precursors and NHC-silver complexes was investigated against Gram-positive bacteria Staphylococcus aureus, and Gram-negative bacteria Escherichia coli using the qualitative Kirby-Bauer disk-diffusion method. NHC-silver complexes have shown very high antibacterial activity compared to the NHC-precursors. All six NHC-silver complexes were tested for their cytotoxicity through MTT based in vitro tests on the human renal-cancer cell line Caki-1 in order to determine their IC?? values. NHC-silver complexes 4a-f were found to have IC?? values of 6.2 (±1.0), 7.7 (±1.6), 1.2 (±0.6), 10.8 (±1.9), 24.2 (±1.8) and 13.6 (±1.0) μM, respectively. These values represent improved cytotoxicity against Caki-1, most notably for 4c, which is a three times more cytotoxic than cisplatin (IC?? value = 3.3 μM) itself.     

Die feldornithologische Kennzeichnung der Tringen

Ohne Zusammenfassung     

SERF protein is a direct modifier of amyloid fiber assembly

The inherent cytotoxicity of aberrantly folded protein aggregates contributes substantially to the pathogenesis of amyloid diseases. It was recently shown that a class of evolutionary conserved proteins, called MOAG-4/SERF, profoundly alter amyloid toxicity via an autonomous but yet unexplained mode. We show that the biological function of human SERF1a originates from its atypical ability to specifically distinguish between amyloid and nonamyloid aggregation. This inherently unstructured protein directly affected the aggregation kinetics of a broad range of amyloidogenic proteins in vitro, while being inactive against nonamyloid aggregation. A representative biophysical analysis of the SERF1a:α-synuclein (aSyn) complex revealed that the amyloid-promoting activity resulted from an early and transient interaction, which was sufficient to provoke a massive increase of soluble aSyn amyloid nucleation templates. Therefore, the autonomous amyloid-modifying activity of SERF1a observed in living organisms relies on a direct and dedicated manipulation of the early stages in the amyloid aggregation pathway.     

Herbivore and pathogen effects on tree growth are additive,but mediated by tree diversity and plant traits

Herbivores and fungal pathogens are key drivers of plant community composition and functioning. The effects of herbivores and pathogens are mediated by the diversity and functional characteristics of their host plants. However, the combined effects of herbivory and pathogen damage, and their consequences for plant performance, have not yet been addressed in the context of biodiversity–ecosystem functioning research. We analyzed the relationships between herbivory, fungal pathogen damage and their effects on tree growth in a large‐scale forest‐biodiversity experiment. Moreover, we tested whether variation in leaf trait and climatic niche characteristics among tree species influenced these relationships. We found significant positive effects of herbivory on pathogen damage, and vice versa. These effects were attenuated by tree species richness—because herbivory increased and pathogen damage decreased with increasing richness—and were most pronounced for species with soft leaves and narrow climatic niches. However, herbivory and pathogens had contrasting, independent effects on tree growth, with pathogens decreasing and herbivory increasing growth. The positive herbivory effects indicate that trees might be able to (over‐)compensate for local damage at the level of the whole tree. Nevertheless, we found a dependence of these effects on richness, leaf traits and climatic niche characteristics of the tree species. This could mean that the ability for compensation is influenced by both biodiversity loss and tree species identity—including effects of larger‐scale climatic adaptations that have been rarely considered in this context. Our results suggest that herbivory and pathogens have additive but contrasting effects on tree growth. Considering effects of both herbivory and pathogens may thus help to better understand the net effects of damage on tree performance in communities differing in diversity. Moreover, our study shows how species richness and species characteristics (leaf traits and climatic niches) can modify tree growth responses to leaf damage under real‐world conditions.     

Triggering the production of the cryptic blue pigment indigoidine from Photorhabdus luminescens

The production of the blue pigment indigoidine has been achieved in the entomopathogenic bacterium Photorhabdus luminescens by a promoter exchange and in Escherichia coli following heterologous expression of the biosynthesis gene indC. Moreover, genes involved in the regulation of this previously “silent” biosynthesis gene cluster have been identified in P. luminescens.     

Analysis of myxobacterial secondary metabolism goes molecular

During the last 20 years myxobacteria have made their way from highly exotic organisms to one of the major sources of microbial secondary metabolites besides actinomycetes and fungi. The pharmaceutical interest in these peculiar prokaryotes lies in their ability to produce a variety of structurally unique compounds and/or metabolites with rare biological activities. This review deals with the recent progress toward a better understanding of the biology, the genetics, the biochemistry and the regulation of secondary metabolite biosynthesis in myxobacteria. These research efforts paved the way to sophisticated in vitro studies and to the heterologous expression of complete biosynthetic pathways in conjunction with their targeted manipulation. The progress made is a prerequisite for using the vast resource of myxobacterial diversity regarding secondary metabolism more efficiently in the future.     

Countershading by physiological colour change in the fish louse Anilocra physodes L. (Crustacea: Isopoda)

Summary Specimens of the fish louse Anilocra physodes L. from the Mediterranean Sea exhibited a striking colour asymmetry in their dorsal pigmentation: one longitudinal half of their back was dark, the opposite half was lightcoloured. The dark side corresponded with the physiological upper side when the fish louse was attached to the flank of a host fish.The colour pattern derives from the different shape (stellate/punctate) of chromatophores, which lie immediately beneath the epidermis. The appearance and distribution of the chromatophore stages indicate the possibility of physiological colour change in Anilocra. In this way the fish louse probably achieves adaptive countershading and thus additional protection from predators, advantageous for both parasite and host.     

Effects of ambient versus reduced UV-B radiation on high arctic Salix arctica assessed by measurements and calculations of chlorophyll a fluorescence parameters from fluorescence transients

A UV-B exclusion-experiment was conducted in the high Arctic Zackenberg, NE Greenland, in which Salix arctica leaves during most of the growing season were fixed perpendicular to the solar zenith angle, thereby receiving maximal solar radiation. Covered with Teflon and Mylar foil, the leaves received approximately 90 and 40% of the ambient UV-B irradiance, respectively. The effects were examined through recordings of chlorophyll a fluorescence transients, determination of biomass and analysis of total carbon and nitrogen content and amount of soluble flavonoids in the leaves. The processing of light was analysed by means of the chlorophyll a fluorescence transient, using the so-called JIP test, as evolved by Reto J. Strasser and his coworkers. Reduction of the UV-B irradiance caused a rise in many of the fluorescence parameters during July, but not in August (late season). Thus increases in the efficiency that an absorbed photon will be trapped by the PSII reaction centre with the resultant reduction of Q_A to Q_A^– (ET₀/ABS = F_V/F_M) and the efficiency that an electron residing on Q_A^– will enter the intersystem electron transport chain (ET₀/TR₀) were observed in reduced UV-B. Moreover, estimated per cross-section of leaf sample, the number of active PSII reaction centres (RC/CS_M) and electron transport rate (ET_M/CS_M) and all performance indexes (PI_ABS, PI_CSo and PI_CSm) were increased in reduced UV-B. The total soluble flavonoid content was highest in ambient UV-B. The treatment effects on fluorescence parameters that were directly measured (e.g. F₀ and F_M) and those that were derived (e.g. quantum efficiencies, parameters per PSII reaction centres and per cross-section of leaf sample) are discussed in relation to one another, in relation to daily and seasonal variation, and from the perspective of evaluating the relative importance of UV-B of donor and acceptor side capacity in Photosystem II. In conclusion, the experimental set-up and non-invasive measurements proved to be a sensitive method to screen for effects of UV-B stress.