22 research outputs found
SynthÚse en série bipyridine. Etude de l'interaction avec l'ADN
rĂ©sumĂ© de la thĂšse en françaisWe have developped the synthesis of heterocycles derived from indolizines and carrying a cationic pyridinium substituent, and studied their interaction with DNA. The key-step of the synthesis of the indolizines is a [3+2] dipolar cycloaddition of ylides formed from quaternary 4,4'-bipyridinium salts with dipolarophiles. The synthesis was done either in classical conditions (solvent, temperature) or by microwave irradiation ("green chemistry"). We have studied the acid-base properties of the bipyridinium salts and their biological activities. The electrical and optical properties along with the photolumiscence of theindolizines are promissing for potential applications as biomedical markers. The interaction of indolizines with DNA was also studied. Finally, we have evaluated the antioxidant properties of indolizines, that have shown an inhibition of peroxidation of vegetal oils in vitro.Nous avons dĂ©veloppĂ© la synthĂšse d'hĂ©tĂ©rocycles indoliziniques fonctionnalisĂ©s par un cation pyridinium et Ă©tudiĂ© leur interaction avec L'ADN. L'Ă©tape-clĂ© pour accĂ©der aux indolizines est la cycloaddition [3+2]-dipolaire des ylures dĂ©rivĂ©s des sels quaternaires de la 4,4'-bipyridine avec des dipolarophiles. La synthĂšse a Ă©tĂ© effectuĂ©e par la voie classique (chauffage en solvant) et par irradiation avec des micro-ondes (âchimie verteâ). Nous avons Ă©tudiĂ© les propriĂ©tĂ©s acido-basiques des sels diquaternaires et leur activitĂ© biologique sur une sĂ©rie de microorganismes. Par ailleurs les propriĂ©tĂ©s Ă©lectriques et optiques ainsi que la photoluminescence des indolizines se sont rĂ©vĂ©lĂ©es prometteuses pour des applications comme les traceurs biomĂ©dicaux. L'interaction des indolizines avec l'ADN a aussi Ă©tĂ© Ă©tudiĂ©e. Finalement, nous avons Ă©valuĂ© les propriĂ©tĂ©s antioxydantes des indolizines, qui ont montrĂ© une activitĂ© inhibitrice de la peroxydation des huiles vĂ©gĂ©tales in vitro
SynthÚse en série bipyridine. Etude de l'interaction avec l'ADN
Nous avons développé la synthÚse d hétérocycles indoliziniques fonctionnalisés par un cation pyridinium et étudié leur interaction avec L ADN. L étape-clé pour accéder aux indolizines est la cycloaddition [3+2]-dipolaire des ylures dérivés des sels quaternaires de la 4,4 -bipyridine avec des dipolarophiles. La synthÚse a été effectuée par la voie classique (chauffage en solvant) et par irradiation avec des micro-ondes ( chimie verte ). Nous avons étudié les propriétés acido-basiques des sels diquaternaires et leur activité biologique sur une série de microorganismes. Par ailleurs les propriétés électriques et optiques ainsi que la photoluminescence des indolizines se sont révélées prometteuses pour des applications comme les traceurs biomédicaux. L interaction des indolizines avec l ADN a aussi été étudiée. Finalement, nous avons évalué les propriétés antioxydantes des indolizines, qui ont montré une activité inhibitrice de la peroxydation des huiles végétales in vitro.We have developped the synthesis of heterocycles derived from indolizines and carrying a cationic pyridinium substituent, and studied their interaction with DNA. The key-step of the synthesis of the indolizines is a [3+2] dipolar cycloaddition of ylides formed from quaternary 4,4'-bipyridinium salts with dipolarophiles. The synthesis was done either in classical conditions (solvent, temperature) or by microwave irradiation ("green chemistry"). We have studied the acid-base properties of the bipyridinium salts and their biological activities. The electrical and optical properties along with the photolumiscence of theindolizines are promissing for potential applications as biomedical markers. The interaction of indolizines with DNA was also studied. Finally, we have evaluated the antioxidant properties of indolizines, that have shown an inhibition of peroxidation of vegetal oils in vitro.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF
FLUORESCENT N-HETEROCYCLES VIA ONE-POT TANDEM REACTIONS
Substituted indolizines are very attractive heterocyclic units. On developing efficient methods toward differently substituted indolizines, we were particularly interested in elaborating efficient approaches toward three-component reaction of these compounds which are very interested from the point of view fluorescent properties. The microwave-mediated three component reaction of acyl bromide, bipyridine and dipolarophyl is catalyzed by basic alumina to give corresponding bis-indolizines in excellent yields in a one âpot reaction
Synthesis and physico-chemical properties of a novel series of aromatic electron acceptors based on N-heterocycles
The synthesis of a novel series of N-based heterocyclic salts using a simple and efficient N-alkylation of 1,2-bis(4-pyridyl)ethane with reactive halides is reported. These compounds can be transformed into the corresponding pyridinium methylides by addition of a base. The former exhibit an unstable absorption bands at 395-410 nm. The structures of the salts were fully characterized by UV-vis, IR, NMR and MS spectroscopy and elemental analysis. The pK values of selected compounds were also determined and the acid basic equilibrium was investigated by UV-vis spectrophotometry. The thermal stability of all species was determined by thermogravimetric analysis. (C) 2012 Elsevier Ltd. All rights reserved
In vitro antimicrobial activity of new nitrogen heterocycles derivates from 4 , 4'-bipyridine.
International audienc
EVALUATION OF THE ANTIMICROBIAL EFFECTS OF NEW HETEROCYCLIC BIS-QUATERNARY AMMONIUM COMPOUNDS ON BIOFILMS
Considering the well-known mechanism of adaptable resistance of microorganisms to chemical compounds through biofilms formation and the widespread use of N-heterocyclic quaternary ammonium salts (QAC) as disinfectants, in this study we have evaluate the effect of 8 newly synthesized symmetrical and unsymmetrical diquaternary ammonium salts of 1,2-bis-(4-pyridil)-ethane on bacterial biofilms produced by three different bacterial strains. The effect of the exposure to quaternary ammonium salts on biofilm communities was investigated within biofilms obtained in a conventional testing system, on stainless steel and glass surfaces. Differential plate counts were used to characterize the developed communities and the effects of QAC exposure and the results were correlated with epifluorescence microphotographs. The data obtained revealed a significant reduction of bacterial cells in the biofilms tested with 4-7 log CFU for all the QAC
Synthesis and in Vitro Antimicrobial Evaluation of New N-Heterocyclic Diquaternary Pyridinium Compounds
A series of bis-pyridinium quaternary ammonium salts (bis-PyQAs) with different aryl and heteroaryl moieties were synthesized and their antimicrobial activity investigated. The inhibition effect of the compounds was evaluated against bacteria, molds and yeasts; the activities were expressed as the minimum inhibitory concentrations (MIC). The relationships between the structure descriptors (logP, polarizability, polar surface area (2D), van der Waals area (3D)) and the biological activity of the tested bis-PyQAs are discussed
Novel One-Pot Green Synthesis of Indolizines Biocatalysed by Candida antarctica Lipases
Marine microorganisms are of considerable interest as a promising source of enzymes with unsuspected potentials as catalysts for chemical synthesis. We describe here an efficient method for one-pot indolizine synthesis that has been developed using lipase A and lipase B from Candida antarctica as biocatalysts. As showed by HPLC/MS analysis, the yield in indolizines was higher in the presence of the biocatalyst than in absence of enzyme. Lipase A, from Candida antarctica, showed high catalytic activity and selectivity for the cycloaddition reactions. When the reactions were performed under ultrasound irradiation, the Candida antarctica lipase catalyzed reactions yielded pure indolozines, in good yields and in very short time
Ăvaluation de lâactivitĂ© anti-inflammatoire et screening phytochimique des feuilles de
Objectif. Cette Ă©tude a pour but de mettre en Ă©vidence lâactivitĂ©
anti-inflammatoire de lâextrait dâĂ©thanol de Annona senegalensis
et de faire son screening phytochimique.
Méthodes. Les rats ont été repartis en trois lots. Le premier lot a reçu uniquement les instillations et injection
saline par voie intrapĂ©rtonĂ©ale pendant les jours J0 et J7. Câest la phase de
sensibilisation des rats de ce lot. Puis, aux jours J21, J22 et J23, les rats du mĂȘme lot
(Lot 1) ont reçu des injections salines sous anesthésie. Le deuxiÚme lot (Lot 2) est
constituĂ© de rats nâayant pas subi de traitement par lâextrait de Annona
senegalensis. Les rats de ce lot ont été sensibilisés par une injection
intrapĂ©ritonĂ©ale (50 ÎŒL) dâune solution dâalbumine (50
ÎŒg/rats) dissoute dans lâhydroxyde dâaluminium, aux jours J0 et J7. Puis,
au cours de la phase de provocation, on a injecté par voie intrapéritonéale une solution
physiologique (saline) contenant 0,9 % de chlorure de sodium Ă une concentration de 1,5 %,
aux jours J21, J22 et J23. Le sacrifice a eu lieu au jour J24, soit 24 heures aprĂšs la
derniĂšre provocation Ă lâovalbumine. De mĂȘme, les rats du troisiĂšme lot (Lot 3) ont fait
lâobjet dâune sensibilisation grĂące Ă lâovalbumine associĂ©e Ă lâhydroxyde dâaluminium aux
jours J0 et J7. Ensuite pendant lâĂ©tape de provocation, les rats de ce lot ont subi
respectivement aux jours J21, J22 et J23, un traitement conjuguĂ© dâalbumine et dâextrait
Ă©thanolique de Annona senegalensis (par injection de 0,4 mL dâextrait par
voie intrapéritonéale en utilisant comme dose 7,10-2 mg/kg). Vingt-quatre
heures aprÚs la derniÚre injection correspondant à J23, les rats ont été sacrifiés sous
anesthésie. Les métabolites secondaires ont été caractérisés par des analyses
physico-chimiques.
Résultats. Les rats du lot témoin (Lot 1) ont donné en
moyenne 24 ± 0,02 mastocytes; 7 ± 0,1 macrophages; 9 ± 0,05 éosinophiles. Dans ce lot
tĂ©moin, la prĂ©sence de neutrophiles nâa pas Ă©tĂ© rĂ©vĂ©lĂ©e. AprĂšs les Ă©tapes de provocation
et de sensibilisation Ă lâalbumine (Lot 2), on a observĂ© une augmentation trĂšs
significative du nombre de cellules inflammatoires par rapport au lot témoin
(p < 0,001). En effet, les mastocytes et les macrophages ont subi respectivement
une augmentation jusquâĂ 164 ± 0,01 et 25 3 ± 0,04. Alors que les Ă©osinophiles ont
augmenté de 9 ± 0,05 à 81 ± 0,01. On a dénombré en moyenne 31 ± 0,02 neutrophiles dans ce
Lot 2. Le Lot 3 traité par Annona senegalensis (7,10-2 mg/kg)
a induit une diminution significative du nombre de cellules inflammatoires par rapport au
lot tĂ©moin (p < 0,001). En effet, les mastocytes ont diminuĂ© de 164 ± 0,01 Ă
89 ± 0,03. De mĂȘme, le nombre de macrophages a diminuĂ© de 253 ± 0,04 Ă 175 ± 0,0 et les
neutrophiles ont diminué de 31 ± 0,02 à 10 ± 0,05. Enfin, les éosinophiles ont subi une
diminution (81 ± 0,01 Ă 61 ± 0,08). Toutefois, aprĂšs le traitement par lâextrait, les
valeurs des différents types cellulaires ont toujours été significativement élevées
(p < 0,001) par rapport à celles du lot témoin (sauf les neutrophiles). Ce résultat
indique que lâextrait de Annona senegalensis nâa pas totalement inhibĂ©
lâeffet inflammatoire induit par lâalbumine.
Les principales classes de métabolites
secondaires, terpénoïdes, coumarines, flavonoïdes et tanins ont été détectées dans les
feuilles de la plante. En revanche, elles sont pauvres en alcaloĂŻdes et en substances
quinoniques.
Conclusion. Lâextrait a induit une diminution significative du
nombre de cellules inflammatoires. Cettte action pourrait sâexpliquer par la prĂ©sence de
mĂ©tabolites secondaires tels que les tanins et les composĂ©s phĂ©noliques dans lâextrait de
plante. Toutefois, son mĂ©canisme dâaction reste encore Ă Ă©lucider
Green âone-potâ fluorescent bis-indolizine synthesis with whole-cell plant biocatalysis
An efficient one-pot route leading to bis-indolizine symmetric compounds has been developed via a new approach from the dipyridinium heterocyclic compound, reactive halogenated derivative, and activated alkyne through biocatalysis. A set of local plants was evaluated for its catalytic potential in âone-potâ biocatalysis of these valuable fluorescent compound synthesis reactions. Most of these biocatalysts containing enzymes from the oxidoreductase class (peroxidase: 0.56â1.08âmmol purpurogallinâ§gâ1 fresh weightâ§minâ1, polyphenol oxidase (PPO) : 27.19â48.95 PPO unitsâ§mg tissueâ1, CAT: 3.27â21.71 ”mol O2â§gâ1 fresh weightâ§minâ1), were used as green catalysts in the multi-component cycloaddition reaction, in an aqueous buffer solution, for the production of bis-indolizine compounds in moderate to excellent yields (45â85%). The horseradish root (Armoracia rusticana) has been selected as the most promising biocatalyst source among the evaluated plants, and the obtained yields were greater than in the conventional synthesis method. The structures of indolizine derivatives were confirmed by nuclear magnetic resonance spectra, elemental analyses, as well as Fourier transform-infrared spectra. The cytotoxicity of the latter obtained indolizine compounds on the growth of the model microorganism, Saccharomyces cerevisiae MIUG 3.6 yeast strain, was also evaluated. Various parameters (number of generations, growth rate, generation time, dry matter yield, the degree of the budding yeast cells, and the degree of yeast autolysis, fermentation intensity), which describe the yeast growth, suggest that the nutrient broth supplemented with different concentrations of bis-indolizine compounds (10 and 1â”M) had no toxic effect on the yeast strain growth, under submerged cultivation conditions