TULIP 4

Tulip is an information visualization framework dedicated to the analysis and visualization of relational data. Based on more than 15 years of research and development, Tulip is built on a suite of tools and techniques , that can be used to address a large variety of domain-specific problems. With Tulip, we aim to provide Python and/or C++ developers a complete library, supporting the design of interactive information visualization applications for relational data, that can be customized to address a wide range of visualization problems. In its current iteration, Tulip enables the development of algorithms, visual encodings, interaction techniques, data models, and domain-specific visualizations. This development pipeline makes the framework efficient for creating research prototypes as well as developing end-user applications. The recent addition of a complete Python programming layer wraps up Tulip as an ideal tool for fast prototyping and treatment automation, allowing to focus on problem solving, and as a great system for teaching purposes at all education levels

Synthèse de nouveaux tétracycles à structure imidazo[4,5-c]pyrrolo[3,2-g]quinoléine, à potentialités antitumorales

L'intérêt antitumoral en particulier comme inhibiteurs de topoisomérases II de molécules planes aromatiques polycycliques telles que les ellipticines, les grossularines et l'amiloride a justifié l'accès à des structures tétracycliques du type imidazo[4,5-c]pyrrolo[3,2-g]quinoléine. Deux voies de synthèse ont été envisagées pour accéder à ces composés, par condensation de guanidines substituées sur des quinoline-2,3,4-triones correctement fonctionnalisées ou par annélation palladocatalysée de N-aryl-2-imidazolylcarboxamides. L'activite cytotoxique et l'effet sur le cycle cellulaire de ces composés ont été évalués sur la lignée de cellules cancéreuses L1210. Les composés les plus actifs sur ce modèle possèdent des CI50 de l'ordre de 3 [micro]M. Les activités inhibitrices sur les Chk-1 et Src kinases, qui sont impliquées respectivement dans le contrôle du point de restriction en phase G2 et dans la transduction du signal, ont aussi été évaluées. Un dérivé des N-(indol-6-yl)-2-(imidazol-5-yl)carboxamides a manifesté une activité significative sur la Src kinase à 1 [micro]M.The antitumoural interest especially as topoisomerase II inhibitors of flat polycyclic aromatic molecules such as ellipticines, grossularines and amiloride has justified to have access to tetracyclic structures of the type imidazo[4,5-c]pyrrolo[3,2-g]quinoline.Two pathways have been considered to give access to these compounds : condensation of substituted guanidines with properly functionalized quinoline-2,3,4-triones and palladium-catalyzed annulation of N-aryl-2-imidazolylcarboxamides. The cytotoxic activity and the effect on the cellular cycle of these compounds have been evaluated on L1210 cancerous cells strain. The most active compounds on this model have IC50 of 3 [micro]M.The inhibitory activities on Chk-1 and Src kinases, which are implicated respectively in G2-phase checkpoint control and signal transduction, have also been evaluated. An N-(indol-6-yl)-2-(imidazol-5-yl)carboxamide derivative showed significant activity on Src kinase at 1 [micro]M.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Cardiotonic steroids on the road to anti-cancer therapy.

The sodium pump, Na(+)/K(+)-ATPase, could be an important target for the development of anti-cancer drugs as it serves as a versatile signal transducer, it is a key player in cell adhesion and its aberrant expression and activity are implicated in the development and progression of different cancers. Cardiotonic steroids, known ligands of the sodium pump have been widely used for the treatment of heart failure. However, early epidemiological evaluations and subsequent demonstration of anti-cancer activity in vitro and in vivo have indicated the possibility of developing this class of compound as chemotherapeutic agents in oncology. Their development to date as anti-cancer agents has however been impaired by a narrow therapeutic margin resulting from their potential to induce cardiovascular side-effects. The review will thus discuss (i) sodium pump structure, function, expression in diverse cancers and its chemical targeting and that of its sub-units, (ii) reported in vitro and in vivo anti-cancer activity of cardiotonic steroids, (iii) managing the toxicity of these compounds and the limitations of existing preclinical models to adequately predict the cardiotoxic potential of new molecules in man and (iv) the potential of chemical modification to reduce the cardiovascular side-effects and improve the anti-cancer activity of new molecules.Journal ArticleResearch Support, Non-U.S. Gov'tReviewinfo:eu-repo/semantics/publishe

A comparative study of the self-immolation of para-aminobenzylalcohol and hemithioaminal-based linkers in the context of protease-sensitive fluorogenic probes.

International audienceThis study focuses on the disassembly-behavior of self-immolative pro-fluorescent linkers under physiological conditions and through an enzyme-initiated domino reaction. The targeted linkers are based on para-aminobenzylalcohol (PABA) or hemithioaminal derivatives of para-carboxybenzaldehyde or glyoxilic acid. We found that a fine tuning of the kinetic properties could be obtained through the modulation of the linker structure, giving either a fast signal response or free-adaptable systems suitable for the design of protease-sensitive fluorogenic probes or prodrug systems

Divergent and regioselective synthesis of 1,2,4- and 1,2,5-trisubstituted imidazoles.

A divergent and regioselective synthesis of 1,2,4- and 1,2,5-trisubstituted imidazoles from a readily available (two steps) common intermediate has been developed. This methodology is based on the regiocontrolled N-alkylation of 1-(N,N-dimethylsulfamoyl)-5-iodo-2-phenylthio-1H-imidazole (10). When this intermediate is engaged in reaction with methyl triflate, selective formation of the corresponding 1,2,5-trisubsituted 1H-imidazole is observed. NMR studies have revealed that this regioselectivity can be accounted for by in situ rapid isomerization of 10 into its 1,2,4-isomer (13) followed by regiospecific N-alkylation of the latter. Conversely, when key intermediate 10 is slowly added to Meerwein's salt, isomerization can be constrained and regiospecific N-alkylation of 10 leads to 1,2,4-trisubstituted 1H-imidazole with a high selectivity. The general character of this methodology has been illustrated by showing that iodine in position 4 or 5 could be easily substituted by an aryl group by Suzuki coupling, whereas the phenylthio group at position 2 could, after oxidation into sulfone, be displaced by nucleophilic substitution

Synthesis and biological evaluation of novel imidazole-containing macrocycles

A new family of compounds made of a 5-aryl-1H-imidazole motif included in a macrocycle has been designed and synthesized. The synthesis of the imidazole core makes use of our previously developed method for the regioselective preparation of 1,2,5-trisubstituted imidazoles while the construction of the macrocycle is based on a three steps sequence: SNAr, Suzuki coupling, and RCM reaction. Biological evaluation of synthesized imidazole-containing macrocycles revealed that they display actual binding activity toward A(3) adenosine (h) receptor, dopamine D-1 (h) receptor, chloride channel (GABA-gated), and choline transporter (h) CHT1. (C) 2010 Elsevier Ltd. All rights reserved

Synthesis and biological evaluation of novel imidazole-containing macrocycles.

info:eu-repo/semantics/publishe

New isocarbostyril alkaloid derivatives.

info:eu-repo/semantics/publishe

Tulip: a Scalable Graph Visualization Framework

National audienc

In Vitro and Ex Vivo Evaluation of Smart Infra-Red Fluorescent Caspase-3 Probes for Molecular Imaging of Cardiovascular Apoptosis

International audiencePURPOSE:The aim of this paper is to develop new optical bioprobes for the imaging of apoptosis.PROCEDURE:We developed quenched near-infrared probes which become fluorescent upon cleavage by caspase-3, the key regulatory enzyme of apoptosis.RESULTS:Probes were shown to be selectively cleaved by recombinant caspase-3. Apoptosis of cultured endothelial cells was associated with an increased fluorescent signal for the cleaved probes, which colocalized with caspase-3 and was reduced by the addition of a caspase-3 inhibitor. Flow cytometry demonstrated a similar profile between the cleaved probes and annexin V. Ex vivo experiments showed that sections of hearts obtained from mice treated with the proapoptotic drug doxorubicin displayed an increase in the fluorescent signal for the cleaved probes, which was reduced by a caspase-3 inhibitor.CONCLUSION:We demonstrated the capacity of these novel probes to detect apoptosis by optical imaging in vitro and ex vivo