Pyrazolo[1,5-a]pyrimidine acetamides: 4-Phenyl alkyl ether derivatives as potent ligands for the 18 kDa translocator protein (TSPO)

Herein, we report the synthesis of four new phenyl alkyl ether derivatives (7, 9–11) of the pyrazolo[1,5-a]pyrimidine acetamide class, all of which showed high binding affinity and selectivity for the TSPO and, in the case of the propyl, propargyl, and butyl ether derivatives, the ability to increase pregnenolone biosynthesis by 80–175% over baseline in rat C6 glioma cells. While these compounds fit our in silico generated pharmacophore for TSPO binding the current model does not account for the observed functional activity.     

A tripartite culture system for endomycorrhizal inoculation of micropropagated strawberry plantlets in vitro

The objective of the current investigation was to develop a reliable method to obtain vesicular arbuscular mycorrhizae (VAM) in micropropagated plantlets and to determine their influence on growth. An in vitro system for culturing the VA mycorrhizal fungus Glomus intraradices with Ri T-DNA-transformed carrot roots or nontransformed tomato roots was used in this study as a potential active source of inoculum for the colonization of micropropagated plantlets. After root induction, micropropagated plantlets grown on cellulose plugs (sorbarod) were placed in contact with the primary mycorrhizae in growth chambers enriched with 5000 ppm CO₂ and fed with a minimal medium. After 20 days of tripartite culture, all plantlets placed in contact with the primary symbiosis were colonized by the VAM fungus. As inoculum source, 30-day-old VA mycorrhizal transformed carrot roots had a substantially higher infection potential than 5-, 10-or 20-day-old VAM. Colonized plantlets had more extensive root systems and better shoot growth than control plants. The VAM symbiosis reduced the plantlet osmotic potential. This response may be a useful pre-adaptation for plantlets during transfer to the acclimatization stage.     

Synthesis of 1'-C-fluoromethyladenosine

In search for new antiviral agents, we have been interested in 1'-C-fluoromethyl branched ribonucleosides. In this paper, we describe the synthesis of 1'-C-fluoromethyladenosine via electrophilic fluorination of exo-glycal.     

Population genetic structure of Tomicus piniperda L. (Curculionidae: Scolytinae) on different pine species and validation of T. destruens (Woll.)

Genetic diversity and population structure of Tomicus piniperda was assessed using mitochondrial sequences on 16 populations sampled on 6 pine species in France. Amplifications of Internal transcribed space 1 (ITS1) were also performed. Our goals were to determine the taxonomic status of the Mediterranean ecotype T. piniperda destruens, and to test for host plant or geographical isolation effect on population genetic structure. We showed that T. piniperda clusters in two mtDNA haplotypic groups. Clade A corresponds to insects sampled in continental France on Pinus sylvestris, P. pinaster and P. uncinata, whereas clade B gathers the individuals sampled in Corsica on P. pinaster and P. radiata and in continental France on P. pinea and P. halepensis. Insects belonging to clade A and clade B also consistently differ in the length of ITS1. Individuals belonging to both clades were found once in sympatry on P. pinaster. Genetic distances between clades are similar to those measured between distinct species of Tomicus. We concluded that clade B actually corresponds to the destruens ecotype and forms a good species, T. destruens. Analyses of molecular variance ( amova ) were conducted separately on T. destruens and T. piniperda to test for an effect of either geographical isolation or host species. Interestingly, the effect of host plant was significant for T. piniperda only, while the effect of geographical isolation was not. Pine species therefore seems to act as a significant barrier to gene flow, even if host race formation is not observed. These results still need to be confirmed by nuclear markers.     

Synthesis of 6-[¹⁸F]fluoro-PBR28, a novel radiotracer for imaging the TSPO 18 kDa with PET

6-Fluoro-PBR28 (N-(6-fluoro-4-phenoxypyridin-3-yl)-N-(2-methoxybenzyl)acetamide), a fluorinated analogue of the recently developed TSPO 18 kDa ligand PBR28, was synthesized and labelled with fluorine-18. 6-Fluoro-PBR28 and its 6-chloro/6-bromo counterparts were synthesized in six chemical steps and obtained in 16%, 10% and 19% overall yields, respectively. Labelling with fluorine-18 was performed in one single step (chlorine/bromine-for-fluorine heteroaromatic substitution) using a Zymate-XP robotic system affording HPLC-purified, ready-to-inject, 6-[¹⁸F]fluoro-PBR28 (>95% radiochemically pure). Non-decay-corrected overall yields were 9-10% and specific radioactivities ranged from 74 to 148 GBq/μmol. In vitro binding experiments, dynamic μPET studies performed in a rat model of acute neuroinflammation (unilaterally, AMPA-induced, striatum-lesioned rats) and ex vivo autoradiography on the same model demonstrated the potential of 6-[¹⁸F]fluoro-PBR28 to image the TSPO 18 kDa using PET.     

Antiviral properties of fucoidan fractions from Leathesia difformis.

Three fractions of fucoidans isolated from the brown seaweed Leathesia difformis (Ee, Ec and Ea) were found to be selective antiviral agents against herpes simplex virus (HSV) types 1 and 2 and human cytomegalovirus. Fraction Ea was the most active, with IC50 values in the range 0.5-1.9 microg/ml without affecting cell viability at concentrations up to 400 microg/ml. The antiherpetic activity of Ea was assessed by three different methods, plaque reduction, inhibition of virus yield and prevention of HSV-2 induced shut-off of cell protein synthesis, demonstrating that the inhibitory effect was independent of the antiviral assay and the multiplicity of infection. The mode of action of Ea could be ascribed to an inhibitory action on virus adsorption. The fucoidans did not inhibit the blood coagulation process even at concentrations exceeding more than 100 times the IC50 value.