Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets

Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. This study describes the synthesis of a series of novel oxadiazoles and indolizine-containing compounds. The compounds were screened in silico using an EIIP/AQVN filter followed by ligand-based virtual screening and molecular docking to parasite arginase. Top hits were further screened versus human arginase and finally against an anti-target battery to tag their possible interactions with proteins essential for the metabolism and clearance of many substances. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three compounds. One compound with an IC50 value of 2.18 mu M on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interesting molecular template for further development of new anti-leishmanial agents

Chimie du saccharose (voie d'accès à des dérivés enrichis en deutérium, à des éthers amphiphiles et à des composés polymérisables)

Le saccharose est le composé organique pur le plus produit dans le monde. Malgré des qualités remarquables (hydrophilie, pureté, biodégradabilité, non-toxicité, provenance de ressource agricoles renouvelables), la quasi-totalité de la production est destinée au secteur de l'agroalimentaire sous une forme non transformée. La synthèse de composés dérivés du saccharose constitue donc un enjeu économique et écologique important. Dans ce but, les méthodes de transformation doivent être respectueuses de l'environnement et d'un coût raisonnable. Les fructo-oligosaccharides (FOS), obtenus par biotransformation du saccharose, sont préparés à l'échelle industrielle et sont commercialisés sous le nom d'Actilight® pour leurs effets comparables à ceux des fibres alimentaires. Dans le but d'étudier le métabolisme des fructo-oligosaccharides, le (6,6,1',1',6',6'-2H6)-saccharose a été synthétisé. Ce produit va permettre l'obtention de fructo-oligosaccharides marqués par des deutériums. Les dérivés tensioactifs du saccharose présentent également un grand intérêt pour l'industrie. Une méthode de préparation d'éthers amphiphiles du saccharose en milieux aqueux a été mise au point. Les facteurs chimiques et physico-chimiques influençant la cinétique de la réaction ont été étudiés. La préparation de monomères hydrophiles, précurseurs des hydrogels, entre également dans le cadre de la valorisation non alimentaire du saccharose. Des alkyl a -D-glucopyranosides fonctionnalisés et polymérisables ont été obtenus à partir de la carboxyméthyl 3,4,6-tri-O-acétyl- a -D-Glucopyranosides 2-O-lactone, obtenue à partit de l'isomaltulose, lui-même produit à l'échelle industrielle en une étape de bioconversion à partir du saccharose.LYON1-BU.Sciences (692662101) / SudocSudocFranceF

Cu I –USY as a Ligand-Free and Recyclable Catalytic System for the Ullmann-Type Diaryl Ether Synthesis

International audienc

Optimising SHJ solar cell bifaciality towards a monolithic module architecture

International audiencethe purpose of this transverse study is to determine the best compromise on cell bifaciality for maximum performance of a monolithic modul

Carboxymethyl glucosides and carboxymethyl glucoside lactones: A detailed study of their preparation by oxidative degradation of disaccharides

International audienceA detailed study of the access to carboxylmethyl tri-O-acetyl-α-d-glucopyranoside 2-O-lactone from isomaltulose was performed. Side products can arise from incomplete oxidation of isomaltulose by hydrogen peroxide, acidic hydrolysis, or opening of the lactone during the acylation step. Based on these observations, the optimum conditions for the preparation of this interesting synthon, as well as of its benzylated and pivaloylated analogues, was determined. Also, the use of the hydrogenated analogue of isomaltulose, isomalt®, as the starting material was studied. In this case, during the oxidation step, the catalysis by sodium tungstate proved to be indispensable to form carboxymethyl glucoside, unlike for isomaltulose. Although giving low yields, this reaction is very direct and was performed using cheap and simple procedures from a readily available substrate.L'étude détaillée de l'accès à la tri-O-acetyl-α-D-glucopyranoside 2-0-lactone à partir d'isomaltulose a été réalisée. Les produits secondaires peuvent provenir de l'oxidation incomplète de l'isomaltulose par le peroxyde d'hydrogène, de l'hydrolyse acide, ou de l'ouverture de la lactone au cours de l'étape d'acylation. En se basant sur ces observations, des conditions optimisées pour la synthèse de cet intéressant synthon ont été déterminées, ainsi que pour la synthèse de ses analogues benzoylés et pivaloylés. Par ailleurs, l'utilisation comme substrat de l'analogue hydrogéné de l'isomaltulose, l'isomalt®, a été étudiée. Dans ce cas, lors de l'étape d'oxydation, la catalyse par le tungstate de sodium s'est révélée indispensable pour former le carboxyméthyl glucoside, contrairement au cas de l'isomaltulose. Bien que les rendements restent modestes, cette séquence est extrêmement directe, et est réalisée à partir de substrats très disponibles

Cu^I–USY as a Ligand-Free and Recyclable Catalytic System for the Ullmann-Type Diaryl Ether Synthesis

The catalytic potential of copper­(I)-exchanged zeolites was evaluated in the Ullmann-type synthesis of diaryl ethers. Among four investigated zeolites (i.e., USY, MOR, β, and ZSM5), Cu^I–USY was the best catalyst and proved efficient under ligand-free conditions in toluene at 120 °C. Cu^I–USY was also easy to recover and was recyclable up to five times without significant loss of activity

Copper(I)–USY as a Ligand-Free and Recyclable Catalyst for Ullmann-Type <i>O</i>‑, <i>N</i>‑, <i>S</i>‑, and <i>C</i>‑Arylation Reactions: Scope and Application to Total Synthesis

The copper­(I)-doped zeolite Cu^I–USY proved to be a versatile, efficient, and recyclable catalyst for various Ullmann-type coupling reactions. Easy to prepare and cheap, this catalytic material enables the arylation and heteroarylation of diverse <i>O</i>-, <i>N</i>-, <i>S</i>-, and <i>C-</i>nucleophiles under ligand-free conditions while exhibiting large functional group compatibility. The facility of this catalyst to promote C–O bond formation was further demonstrated with the total synthesis of 3-methylobovatol, a naturally occurring diaryl ether of biological relevance. From a mechanistic viewpoint, two competitive pathways depending on the nature of the nucleophile and consistent with the obtained results have been proposed

Novel lipophilic 7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid derivatives as potential antitumor agents: Improved synthesis and in vitro evaluation.

A convenient route for the synthesis of some acyloxymethyl esters and carboxamides of levofloxacin (LV) with modulated lipophilicity is described. The synthesized compounds were evaluated in vitro for their growth inhibitory effect in five human cancer cell lines. The most efficient LV derivatives (ester 2e and amide 4d) displayed IC(50) values in the 0.2-2.2μM range, while IC(50) values for parent LV ranged between 70 and 622μM depending on the cell line. The esters displayed no in vivo toxicity up to 80mg/kg when administered intraperitoneally. This study thus shows that LV analogs displayed antitumor efficacy, at least in vitro, a feature that appeared to be independent from the lipophilicity of the grafted substituent.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Recommendations for the prescription, implementation and interpretation of medical examinations in biology in the context of severe poisoning

International audienc