Photodynamic effects of porphyrin-polyamine conjugates in human breast cancer and keratinocyte cell lines

Porphyrin-polyamine conjugates bearing two (cis or trans position) or four spermidine or spermine units were synthesized. We studied the photostability, the hydrophilic/lipophilic balance of porphyrin-polyamine derivatives and the production of singlet oxygen. All these compounds possess physicochemical features required for their use in PDT. Then, we investigated the photocytotoxic efficacy of these porphyrin-polyamine derivatives and the cell death pathway implicated. All compounds appear to be more efficient than Photofrin? to induce HaCat and MCF7 cell death, essentially by apoptosis. Collectively, these data show that porphyrin-polyamine conjugates could be promising phototherapeutic agents.     

Synthesis and physicochemical characterization of new squalenoyl amphiphilic gadolinium complexes as nanoparticle contrast agents

A family of novel amphiphilic gadolinium chelates was successfully obtained by coupling the hydrophilic DOTA ligand [1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane] to squalenoyl moieties. Thanks to the self-assembling properties of their squalenoyl lipophilic moieties, all these derivatives were able to form, without any adjuvant, micellar or liposome-like supramolecular nanoassemblies, endowed with high relaxivities (r(1) = 15-22 mM(-1) s(-1) at 20 MHz and 37 °C). The remarkably high payloads of Gd(3+) ions reached 10 to 17 wt %. Moreover, one of these derivatives interacted with human serum albumin (HSA) forming mixed micelles, which induced a remarkable increase in relaxivity. Liposome-like structures were obtained when the Gd(3+) complex of DOTA was coupled to two squalene units. These liposomal structures were characterized by a high loading of Gd(3+) (about 74,000 gadolinium ions per particle of 100 nm). The supramolecular architecture of these nano-objects has been investigated by electron microscopy and small-angle X-ray scattering. Squalenoylation of gadolinium derivatives offers a platform to conceive contrast agents (CAs) in mild conditions (no toxic solvents, no surfactants, no energy input). These new amphiphilic gadolinium chelates could also find potential applications in theranostics, by forming mixed systems with other squalenoylated drugs, or to delineate blood vessels owing to the interaction with HSA.     

N-free orders and minimal interval extensions

We investigate problems related to the set of minimal interval extensions of N-free orders. This leads us to a correspondence between this set for an arbitrary order and a certain set of its maximal N-free reductions. We also get a 1-1-correspondence between the set of linear extensions of an arbitrary order and the set of minimal interval extensions of the linegraph of that order. This has an algorithmic consequence, namely the problem of counting minimal interval extensions of an N-free order is #P-complete. Finally a characterization of all N-free orders with isomorphic root graph is given in terms of their lattice of maximal antichains; the lattices are isomorphic iff the root graphs agree.This work was supported by the PROCOPE Program. The first author is supported by the DFG.     

Hypersurfaces with constant mean curvature in hyperbolic space form

In this article, we prove the following theorem: A complete hypersurface of the hyperbolic space form, which has constant mean curvature and non-negative Ricci curvature Q, has non-negative sectional curvature. Moreover, if it is compact, it is a geodesic distance sphere; if its soul is not reduced to a point, it is a geodesic hypercylinder; if its soul is reduced to a point p, its curvature satisfies Q<, and the geodesic spheres centered at p are convex, then it is a horosphere.A part of this work has been done when the second author visited Université Claude Bernard Lyon 1, and was supported by a grant of the People's Republic of China.     

Synthesis of 1,3,4-thiadiazin-2-one and 1,3,4-selenadiazin-2-one derivatives as new cardiotonic drugs

The synthesis of the new heterocycle 1,3,4-selenadiazin-2-one is described, based on the preparation of the analogue heterocycle 1,3,4-thiadiazin-2-one. The related cyclization between an α-haloketone and a thiocarbazate cannot readily be employed within the selenium series. Therefore a new route was developed based upon a diazotization/hydrolysis sequence of the related 2-amino-1,3,4-selenadiazine.     

New strategies for cyclization and bicyclization of oligonucleotides by click chemistry assisted by microwaves

The synthesis of cyclic, branched, and bicyclic oligonucleotides was performed by copper-catalyzed azide-alkyne cycloaddition assisted by microwaves in solution and on solid support. For that purpose, new phosphoramidite building blocks and new solid supports were designed to introduce alkyne and bromo functions into the same oligonucleotide by solid-phase synthesis on a DNA synthesizer. The bromine atom was then substituted by sodium azide to yield azide oligonucleotides. Cyclizations were found to be more efficient in solution than on solid support. This method allowed the efficient preparation of cyclic (6- to 20-mers), branched (with one or two dangling sequences), and bicyclic (2 x 10-mers) oligonucleotides.     

Synthesis of Homo- and Heterofunctionalized Glycoclusters and Binding to Pseudomonas aeruginosa Lectins PA-IL and PA-IIL

Homo- and heterofunctionalized glycoclusters with galactose and/or fucose residues targeting both PA-IL and PA-IIL lectins of Pseudomonas aeruginosa were synthesized using "Click" chemistry and DNA chemistry. Their binding to lectins (separately or in a mixture) was studied using a DNA Directed Immobilization carbohydrate microarray. Homoglycoclusters bind selectively to their lectin while the heteroglycocluster binds simultaneously both lectins with a slight lower affinity.     

Impact of glycosylation on physico–chemical and biological properties of nitrification inhibitors

The lipophilic 2-mercaptobenzothiazole (MBT), known for its nitrification inhibition properties, was derivatized thanks to direct glycosylation reactions. Similar transformations were also performed starting from 2-mercaptobenzimidazole (MBI), structurally close to MBT. The resulting S-linked mono- or disaccharides derived from d-glucose or l-arabinose, and cellobiose, gentiobiose or lactose, respectively, were subsequently studied as novel nitrification inhibitors without any further formulation or physical processes, except dilution in water. Along with ecotoxicity measurements, inhibition properties of the synthesized water soluble glycoconjugates were studied in a model reactor containing nitrification bacteria. The best results were obtained for the gentiobiosyl derivatives simply dissolved in water.     

Microwave assisted "click" chemistry for the synthesis of multiple labeled-carbohydrate oligonucleotides on solid support

A versatile approach has been developed for the multiple labeling of oligonucleotides. First, three linkers as a H-phosphonate monoester derivative were condensed on a solid-supported T12 to introduce H-phosphonate diester linkages which were oxidized in the presence of propargylamine. Second, three galactosyl azide derivatives were conjugated to the solid-supported three-alkyne-modified T12 by a 1,3-cycloaddition so-called "click chemistry" in the presence of Cu(I) assisted by microwaves.