Star-pseudopolyrotaxane organized in nanoplatelets for poly(ε-caprolactone)-based nanofibrous scaffolds with enhanced surface reactivity.

Herein, it is demonstrated that star pseudopolyrotaxanes (star-pPRs) obtained from the inclusion complexation of α-cyclodextrin (CD) and four-branched star poly(ε-caprolactone) (star-PCL) organize into nanoplatelets in dimethyl sulfoxide at 35 °C. This peculiar property, not observed for linear pseudopolyrotaxanes, allows the processing of star-pPRs while preserving their supramolecular assembly. Thus, original PCL:star-pPR core:shell nanofibers are elaborated by coaxial electrospinning. The star-pPR shell ensures the presence of available CD hydroxyl functions on the fiber surface allowing its postfunctionalization. As proof of concept, fluorescein isothiocyanate is grafted. Moreover, the morphology of the fibers is maintained due to the star-pPR shell that acts as a shield, preventing the fiber dissolution during chemical modification. The proposed strategy is simple and avoids the synthesis of polyrotaxanes, i.e., pPR end-capping to prevent the CD dethreading. As PCL is widely used for biomedical applications, this strategy paves the way for simple functionalization with any bioactive molecules.

Benzopyridooxathiazepine derivatives as novel potent antimitotic agents.

Herein, we describe the structure-activity relationship study of a new 1-(arylalkyl)-11H-benzo[f]-1,2-dihydropyrido[3,2,c][1,2,5]oxathiazepine 5,5-dioxide series of antimitotic agents. The pharmacological results obtained from previous works allowed us to identify compound 1 as a new cytotoxic agent inhibiting tubulin polymerization. We have undertaken the synthesis of its non-methylated analogue 7 and have extended our investigations to a novel, structurally related benzopyridooxathiazepine dioxide series. Among all analogues synthesized in this study, compound 10b was the most promising, being 12-fold more potent than compound 1. Its activity over a panel of five tumoral cell lines was in the nanomolar range for all of the histological types tested and flow cytometric studies performed on L1210 cells showed an accumulation of the cells in the G2/M phases of the cell cycle with a significant percentage of tetraploid cells (8N DNA content). This interesting pharmacological profile, resulting from inhibition of tubulin polymerization, encouraged us to perform preliminary in vivo studies.

Novel benzopyridothiadiazepines as potential active antitumor agents.

The synthesis of novel thiadiazepine derivatives, that could be considered as constraint analogues of E-7010, are reported. These molecules were evaluated for their antiproliferative activity toward the murine L1210 leukemia cell line. Flow cytometric studies performed on L1210 cells with the most cytotoxic compounds showed an accumulation of the cells in the G2/M phases of the cell cycle with a significant percentage of tetraploid cells (8N DNA content). Submicromolar cytotoxicities were observed with compounds 2b, 4b, 4e, 4g, and 4i. Two of them, compounds 2b and 4b, were found to be potent inhibitors of tubulin polymerization with IC50 of respectively 3.8 and 2.4 microM compared to 2.4 microM for desoxypodophyllotoxin. A 4-methoxyphenylethyl substitution on the pyridinyl nitrogen of the benzopyridothiadiazepine was found to be essential for the antiproliferative activity. The in vitro activities of compounds 2b and 4b make benzopyridothiadiazepine dioxides a promising new class of tubulin binders which warrant further in vivo evaluation.

Responses of three heathland shrubs to single or repeated experimental trampling.

In the last few decades, trampling has become a cause of major disturbance to natural areas. Trampling can occur regularly either seasonally or throughout the year, or as a single impact depending on a recreational activity or an event. This study, carried out on a coastal heathland in north Brittany (France), was based on the hypothesis that the vegetation response can differ depending on whether the trampling is repeated or due to a single event. The aim was to compare the resistance and the short-term recovery capacity of selected species in coastal heathland communities subjected to a trampling experiment, applied once or five times (with equal total number of passes from 0 to 800). The temporal distribution of the trampling did not affect the response of Erica ciliaris, whereas for Erica cinerea and Ulex gallii, trampling was slightly less damaging when applied once rather than five times. These differences could be linked to the lower resistance and the higher recovery capacity of E. ciliaris, compared with the two other species. This study also emphasized the influence of site location by comparing observations with previous studies. Plant resistance calculated here appeared to be lower than that calculated for a less stressful site. The relationship between plant traits and response to trampling was also investigated. The effects of the different times between disturbance application and observations of the short-term response of woody vegetation to experimental trampling is also discussed.

Comparison of the vegetation and seed bank on hedge banks of different ages in Brittany, France.

The composition of the herbaceous cover and the seed bank of old and recent hedge banks in Brittany were studied and compared. Concentration method was used for seed bank samples. Grime's plant strategies were used to explain observed patterns. The analysis of the seed bank of these hedge banks showed that the species richness and diversity differed in relation to the date of construction of the hedge banks. The seed banks of recent hedge banks were richer and more diversified than those of old hedge banks. Differences in the floristic composition of the established plant cover between the recent and old hedge banks were determined by multivariate analyses. The species exclusively found in the seed bank and in the herb cover of recent hedge banks were mainly grassland species, whereas the species that only occurred on old hedge banks tended to be woodland species. The floristic composition of the two compartments (established vegetation and seed bank) was very different. A multivariate analysis revealed that the difference between the composition of the seed banks of recent and old hedge banks was less than that between the composition of the established vegetation and seed bank of hedge banks of the same age. Both seed bank and vegetation of recent hedge banks were dominated by ruderal species, whereas old hedge vegetation was dominated by stress-tolerant woodland species, indicating that mechanically constructed hedge banks may impose limitations on colonization by late woodland species.

Docking study of ligands into the colchicine binding site of tubulin.

Cancer is a major cause of mortality in developed countries, following only cardiovascular diseases. Death of cancerous cells can be achieved by stopping mitosis and the antimitotic class of drugs formed by the spindle poisons can be used for this purpose. Their role is to disorganize the mitotic spindle by targeting its main constituent, the microtubules, themselves made of heterodimers of alpha and beta-tubulin. They disrupt the dynamics of the microtubules either by stabilizing them, as do paclitaxel or epothilones, or destabilizing them, as do colchicine. The binding site of colchicine seems to lie between the two units of the tubulin dimer. Here, we report on the characterization of this site by the docking of a series of reference compounds, and the subsequent docking of ligands prepared in our laboratory.

Sustainable management of fixed dunes: example of a pilot site in Brittany (France).

The sand-dunes of Quiberon was chosen as a pilot site to investigate experimentation in conservatory management. Sand burial is necessary to conserve the semi-fixed dune which is a transitory dynamic stage. In the fixed dune, low disturbances benefit the vegetation diversity while heavy ones create serious injury. An opening of the milieu can restore very fast but a naked substrate is difficult to heal. The deposition of gorse branches is then efficient to facilitate the restoration. The fixed dune biodiversity is linked to human activities. Disturbances, natural or not, may be used as management tools.