Дисертації з теми "Podophyllotoxine – analogues et dérivés"
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Mouton, Carole. "La podophyllotoxine et ses dérivés inhibant la polymérisation de la tubuline et/ ou l'ADN-topoisomérase II." Paris 5, 1994. http://www.theses.fr/1994PA05P153.
Nguyen, Dinh Vu. "Synthèse de composés antidépresseurs et anticancéreux - Contribution méthodologique à la réactivité des époxydes et des dérivés organiques du bismuth." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS374/document.
My PhD thesis mainly involves the enantioselective synthesis of the Milnacipran's analog, a trisubstituted cyclobutane bearing two contiguous stereogenic centers. We have devised a conventional approach which consists of an intramolecular SN2 cyclization. After an acidic treatment, the key intermediate lactone was isolated with an ee > 99%, which was converted to the Milnacarre with no erosion of the ee value. We have also interested in the nanometric formulation of Podophyllotoxine derivatives. The natural product was designed to bear a hydrophilic and hydrophobic side chain. Its micellar solution was evaluated in vitro, in vivo and the obtained resuls were shown to be promising.We have also studied two methodologies: the reactivity of glycidyl ether toward alkyllithium reagents and oxydation of hydroxylamines to nitrone using triphenylbismuth carbonate. We observed in the former case an original rearrangement of the substrate to a vicinal diol, while in the latter case we have developped a mild condition to perform an tandem oxydation/1,3-dipolar cycloaddition in situ with a strained alkyne
Aillerie, Alexandre. "Organocatalyse : réduction asymétrique par transfert d’hydrogène et synthèse de nouveaux catalyseurs." Thesis, Lille 1, 2014. http://www.theses.fr/2014LIL10185.
The control of chirality is crucial in the synthesis of chiral active biologically molecules. Numerous chiral tetrahydroquinolines have revealed outstanding biological activities, particularly in the treatment of cancer. One of the asymmetric reduction systems to access these compounds of medicinal interest combines an organic hydride source and a chiral Brønsted acid catalyst. This system is based on a biomimetic approach of NADH and NADPH cofactors involved in many redox metabolisms. Following this methodology in agreement with the sustainable development, various enantiopure nitrogen-based heterocycles have been prepared as potential anticancer drugs. The first enantioselective synthesis of 4-azapodophyllotoxine derivatives using this reduction process has been set up. An innovative methodology, based on the possibility to generate in situ the hydride source has also been developed. Moreover, news organocatalysts derived from phospholanic acid and ferrocene have also been synthesized and evaluated within chemical transformations
Meneyrol, Jérôme. "Synthèse de nouveaux hétérolignanes dérivés de la podophyllotoxine en séries 1-Aza et 4-Aza." Paris 5, 2001. http://www.theses.fr/2001PA05P626.
Schmitt, Benoît. "5,6,7,8-tétrahydro-1,6-naphtyridines : dérivés et analogues structuraux." Université Louis Pasteur (Strasbourg) (1971-2008), 2004. http://www.theses.fr/2004STR13210.
Maiga, Soufiana. "Synthèse et études photobiologique et pyronocoumarines, analogues des psoralènes." Paris 11, 1991. http://www.theses.fr/1991PA114843.
MERESSE, PHILIPPE. "Conception, synthese et evaluation biologique d'agents antitumoraux : analogues structuraux de l'etoposide, de la podophyllotoxine et de la 4-demethylepipodophyllotoxine." Paris 6, 2000. http://www.theses.fr/2000PA066327.
Simon, Gaëlle. "Analogues et dérivés des méridianines : Synthèse et Étude structure-activité biologique." Brest, 2004. http://www.theses.fr/2004BRES2011.
The marine environment constitues a very promising source for novel and bioactive molecules, and meridianins have been identified among those recently discovered. These indoles with a 2-aminopyrimidine at C-3 can inhibit cyclin-dependent kinases. In order to conduct additionnal biological tests about these 3-(2-aminopyrimidine)indoles, we first synthesised NH meridianin-analogues through two routes: (i) a Miyaura-Suzuki coupling of indol-3-ylboronic acids to 2-amino-4-chloropyrimidine, and (ii) the formation of a 2-amino-pyrimidine by guanidine condensation with enaminones issued from the reaction of N,N-dimethylformamide dimethylacetal (DMF-DMA) with 3-acetylindoles. Then, in a second stage we prepared N-alkyled derivatives of meridianins by applying the same linear synthesis, using pyrrolidine for the formation of enaminones. At last, various derivatives were prepared by replacing the indole with the 1,2,3,9-tetrahydro-4H-carbazol-4-one cycle or using various pyrimidines. Some of these molecules were finally tested against cyclin-dependent kinases (GSK-3 and CDK1) and cell lines (RAJI, DAUDI and K562) as part of cancer-related researches. Other tests about the fixation of barnacle larvae were also performed to investigate the antifouling properties of these new molecules
Bayrakdar, Hassan. "Synthèse et activité biologique (spectre antibactérien, inhibition de l'ADN gyrase) d'analogues ouverts et monocycliques des quinolones." Nancy 1, 1992. http://docnum.univ-lorraine.fr/public/SCD_T_1992_0428_BAYRAKDAR.pdf.
Duca, Maria. "Nouveaux inhibiteurs de topoisomérase II dérivés de la 4'-déméthylépipodophyllotoxine dirigés sur des séquences spécifiques de l'ADN : conception, synthèse et applications." Paris, Muséum national d'histoire naturelle, 2005. http://www.theses.fr/2005MNHN0008.
DNA topoisomerase II is an ubiquitous and essential enzyme that modulates DNA topology by passing an intact DNA double helix through a transient double-stranded break. This enzyme plays critical roles in a number of DNA processes. Topoisomerase II is the primary cellular target for a large number of anticancer agents, like 4'-demethylepipodophillotoxin derivatives. These molecules stabilise the DNA/TopoII complex, and induce DNA breaks. This action converts topoisomerase II into a potent cellular toxin that fragments the genome and induces cell death. Among 4'-demethylepipodophyllotoxin derivatives, etoposide is widely used in anticancer therapy, however it presents several limitations, such as poor water solubility, development of drug resistance, metabolic inactivation and toxic effects. Therefore, we synthesized new series of etoposide analogs by introducing different substituents in 4-position, like carbamate or sulfonamide chains. Then we evaluated the effect on topoisomerase II and the cytotoxicity. The conjugation of antitumor agents, such as topoisomerase I inhibitors, allowed to direct the cleavage mediated by topoisomerase I to specific sites of the genome. On this basis we synthesized new conjgates between the new topoisomerase II inhibitors and triplex forming oligonucletides (TFO) and evaluated their ability to recruit topoisomerase II and direct its cleavage to specific DNA sequences. This targeting strategy allows to obtain topoisomerase II-mediated DNA cleavage at specific sequences of DNA, like a gene involved in cancer development. We choose to target mdr1 gene which is responsible of multidrug resistance. We obtained the inhibition of its expression by using a conjugate TFO-daunorubicine. These conjugates are also a biochemical tool to study the molecular mechanism of action of etoposide and its analogs
Colacino, Evelina. "Synthèse et étude de nouveaux analogues de nucléosides pyrimidiques modifiés sur la base hétérocyclique." Montpellier 2, 2002. http://www.theses.fr/2002MON20074.
Chioua, Rachid. "Synthèse, structure et réactivité de dérivés de la 1H-pyrazolo[3,4-c]pyridine. Analogues acycliques de nucléosides." Montpellier 1, 1992. http://www.theses.fr/1992MON13526.
Charbonnier, Florence. "Synthèses, études structurales et propriétés de complexation d'Ureido-oligosaccharides supramoléculaires." Nancy 1, 1999. http://www.theses.fr/1999NAN12008.
Janin, Yves. "Analogues et dérivés inédits des benzo[c]phénanthridines antitumorales. Synthèse et étude biologique." Phd thesis, Université Pierre et Marie Curie - Paris VI, 1993. http://tel.archives-ouvertes.fr/tel-00175198.
- La découverte d'une nouvelle méthode de synthèse des alcoxy-1-aminonaphthalènes à partir des 1-tétralones correspondantes. A partir de ces amines, la généralisation d'une voie d'accès aux 7,8,9,10-tétrahydro benzo[c]phénanthridin-6(5H)-ones nous a permis de synthétiser 16 dérivés des benzo[c]phénanthridines mono ou bifonctionnalisées.
- Une étude de la voie d'accès aux benzo[c]phénanthridines selon Robinson a été réalisée pour préparer les analogues tétraoxygénés. A ce sujet, nous avons trouvé des conditions de préparation de 2-aryl-1-aminonaphthalènes, jamais décrites auparavant, à partir de 2-aryl-1-tétralone oximes utilisant la réaction de Semmler-Wolff. Au départ de ces amines nous avons pu préparer les uréthanes correspondants, dont la cyclisation thermique engendre les benzo[c]phénanthridin-6(5H)-ones, facilement transformées en dérivés 6-chlorés. Tandis que la substitution de ces derniers par les amines conduit aux analogues tétraoxygénés, cette synthèse correspond aussi, formellement, à une nouvelle voie d'accès aux alcaloïdes de cette famille.
- Par ailleurs, la condensation entre la 6-méthoxy-1-tétralone, le propiolate de méthyle et l'ammoniac qui conduit à la 8-méthoxy-5,6-dihydrobenzo[h]quinoléin-2(1H)-one a permis de préparer quatre dérivés du noyau benzo[h]quinoléine substitués en position 2 par les mêmes chaînes aminées que ci-dessus.
Les résultats des tests de cytotoxicité effectués pour l'ensemble des dérivés aminés, de même que l'activité antitumorale de certains d'entre eux, sont décrits.
Benjahad, Abdellah. "Synthèse, analyse structurale et évaluation antivirale de nouveaux analogues de nucléosides de types pyrazinique et pipérazinique." Limoges, 1996. http://www.theses.fr/1996LIMO0011.
Gulberti, Sandrine. "Caractérisation structurale et fonctionnelle de la galactose-bêta1,3-glucuronosyltransférase-I recombinante humaine (GlcAT-I)." Nancy 1, 2003. http://www.theses.fr/2003NAN12503.
Mathieu, Romain. "Dérivés d'adénines et pyrazolotriazines isostères : synthèses et relations structure-activité." Strasbourg 1, 2004. http://www.theses.fr/2004STR13219.
The adenine derivatives are widely distributed in nature and regulate a broad range of cell functions. We have first focused our interest on the adenine derivatives substituted at the 2-position in order to develop new P2Y1 receptor antagonists. Various 2-substituted derivatives of MRS-2179 (N6-methyl-2'-deoxyadenosine-3',5'-bisphosphate) have been synthesized with the goal to better understand structure-activity relationships around this position. Thus, we have adopted a chemical pathway using a selective 2-stannylation of 6-chloropurine on the 2'-deoxyadenosine scaffold, for an efficient synthesis of the 2-iodo intermediate (5 steps, 18% overall yield). Then, the palladium-catalyzed cross-coupling reactions allowed us to introduce various substituents at 2-position in high yields. Finally, the hydroxyls 3' and 5' were phosphorylated to afford the desired nucleotides. This topological exploration of the P2Y1 receptor highlighted a medium hydrophobic pocket which tolerated alkyl substituents until propyl. The 2-ethynyl derivative (LPI-448) was 10-fold more potent than the reference MRS-2179 and strongly inhibited in vitro platelet aggregation. Then, we continued this exploration by means of an isosteric pyrazolo[1,5-a]-1,3,5-triazines series in order to discover new interactions. Various substituents (functional groups linked to the heterocycle by an alkyl chain of variable length) were introduced at 8-position in good yields through Sonogashira and Heck cross-coupling reactions. Among this series, ten derivatives strongly inhibited PDE-4 and the lead compound (LPI-444) exhibited remarkable properties (IC50 = 31 nM and excellent PDE-1, 2, 3, 5 selectivities)
Auguste, Marie-Laure. "Synthèses de dérivés nucléosidiques en série triazole et à conformation restreinte à visée antitumorale." Montpellier 2, 2007. http://www.theses.fr/2007MON20176.
Rycke, Nicolas de. "Nouveaux analogues de la DMAP : synthèse et réactivité." Versailles-St Quentin en Yvelines, 2011. http://www.theses.fr/2011VERS0024.
Catalysts which act as Lewis bases show a growing interest because of their capacity to promote a significant number of transformations in organic synthesis. Specifically, since its discover at the end of the 1960’s, 4-(dimethylamino)pyridin (DMAP) has been studied and introduced to accelerate the rate of several reactions such as the acylation of tertiary alcohols. The reactivity of this derivative is sometimes limited with deactivated substrates leading to a very slow conversion in products. First, we were interested on the synthesis of tricyclic triaminopyridins, strong analogs of DMAP and their reactivity was studied with the determinations of kinetic N and Lewis parameters thermodynamic basicity. Secondly, we prepared a new class of chiral DMAP derivatives, the structure of which is included in a paracyclophanic backbone. In parallel to this work, we developed a new nucleophilic probe which was involved in the comparison of the reactivity of aziridinium and azetidinium towards nucleophiles, by measuring their ring opening rates by UV-visible and RMN 1H spectrophotometry. Finally, the last part of this pH. D. Work was about the design and the synthesis of organocatalytic cages. This kind of derivatives would encapsultate substrates within its cavity to promote chemical reactions like enzymes do, while avoiding their difficulties of use such as a limited stability under certain protocols
Zgani, Ibrahim. "Synthèse et évaluation biologique de nouveaux analogues de pyrophosphates de prényles." Montpellier 2, 2001. http://www.theses.fr/2001MON20077.
Labssita, Youssef. "Conception et synthèse de nouveaux dérivés benzopyroniques et de leurs analogues comme ligands des récepteurs sigma." Toulouse 3, 1996. http://www.theses.fr/1996TOU30025.
Salmi, Chanaz. "Conception et évaluation des activités antimicrobiennes de nouveaux dérivés aminostéroïdiens analogues de la squalamine." Aix-Marseille 3, 2007. http://www.theses.fr/2007AIX30028.
Extensive use of antibiotics has raised a serious public health problem due to infections caused by multidrug-resistant bacterial pathogens. Consequently, there is a pressing need to develop new antibiotics to keep pace with bacterial resistance. Recently, a new cationic sterol, squalamine has been isolated from tissues of the dogfish shark Squalus Acanthias exhibiting potent antimicrobial activities. The synthesis of numerous squalamine analogues has been realized involving a diastereoselective titatium reductive amination reaction developed in our laboratory. A structure–activity relationships study has been conduced in order to determine the influence of polyamino, hydroxyl and sulfate moieties on the encountered antimicrobial activities
Fougère, Cécile. "Nouvelle méthode de synthèse de dérivés phosphiniques : Application à la synthèse de nouveaux biomimétiques dérivés de peptide et de PNA." Paris 13, 2009. http://www.theses.fr/2009PA132017.
The use of oligonucleotides and peptides as more selective drug is a new strategy more and more studied to treat several diseases. However the main drawback in the use of these macromolecules as therapeutic agent is their poor stability in biological media. A solution could be to synthesize mimetic with improved properties. In our work we focused on the development of oligonucleotide mimics: peptide nucleic acids PNA and on peptide mimic. For these two mimics we choose to replace amide bond in the peptidic or pseudopeptidic structure by a phosphinic linkage, in order to increase for the peptide the stability towards enzymatic degradation and for the PNA to increase the aqueous solubility. First, we developed a new methodology for the obtaining of asymmetric phosphinic acids (R’P(O)OHR’’). This new synthetic strategy is carry out in mild conditions which allowed the use of functionalized substrates. We then apply this methodology to the synthesis of a simple dipeptide Gly[P(O)(OH)CH2]Gly and secondly of a dipeptide Ala[P(O)(OH)CH2]Ala. We evaluated the incorporation of this later dipeptide in the sequence of an antiangiogenic peptide (A-p-AWLPPR). The last aspect of this work was to study several strategies for the obtaining of a phosphinic dimer synthon of PNA: TpT which could be introduced in diverse position in a PNA sequence (TTTTCTTTT): the sequence of HIV-1 polypurin Tract (PPT) RNA
Mialhe, Samuel. "Synthèse et étude de 2'-C-méthyl-β-D-ribonuléosides à visée anti-hépatite C : dérivés de l'imadazole, dérivés puriques modifiés en position 6, analogues 5'-phosphonates". Montpellier 2, 2005. http://www.theses.fr/2005MON20158.
Pierra, Claire. "Analogues nucléosidiques et pronucléotides inédits d'anomérie Bêta et d'énantiomérie non naturelle L : synthèse et propriétés antivirales de dérivés de l'adénosine, de la 5-chlorouridine et de la 5-chlorocytidine." Montpellier 2, 1997. http://www.theses.fr/1997MON20135.
Levkov, Igor. "Réactivité du 1-aminoisoindole, de ses dérivés et analogues : action des diénophiles en milieu homogène et structuré." Toulouse 3, 2013. http://thesesups.ups-tlse.fr/2054/.
With the Curtin-Hammett principle for the first time isoindoles which are mainly exist in the isoindoline tautomeric form were introduced into the reaction with cyclic dienophiles and the products of these reactions were obtained. We synthesized a series of surfactantson the basis of isoindoles with long alkyl chains and studied their physico-chemical properties of aggregation in water and formamide. The reactivity of 1-aminoisoindole was compared in homogeneous and structured media. It has been shown that structured environment can act as a catalyst in the interaction with maleimides. In the case where the concentration of amphiphilic derivatives of aminoisoindole is lower than the critical aggregation concentration (homogeneous medium), the reaction with maleimide does not happen. We proposed two new methods of the synthesis of fluorescent derivatives of 4-aminobenzo[f]isoindole which have some advantages over described in the literature including the velocity of the reaction, simple way of obtaining products with high purity and better yields
Correia, José. "Synthèse, caractérisation et propriétés de copolymères dérivés du poly(chlorure de vinyle) analogues a l'héparine." Paris 13, 1995. http://www.theses.fr/1995PA132035.
Lepretre, Jean-Claude. "Synthèse et étude électrochimique de sels de pyridinium 3,5- disubstitués modèles du NAD+ : réactivité et comportement de leurs analogues réduits." Grenoble 1, 1992. http://www.theses.fr/1992GRE10032.
Battaglia, Eric. "Contribution d'inhibiteurs compétitifs, de sondes électrophiles et de marqueurs de photoaffinité à l'étude du site actif de l'UDP-glucuronosyltransférase recombinante humaine UGT1*6 (conjugaison des composés phénoliques plans)." Nancy 1, 1993. http://docnum.univ-lorraine.fr/public/SCD_T_1993_0434_BATTAGLIA.pdf.
Storme, Thomas. "Conception, synthèse et évaluations d'analogues de l'ifosfamide à moindres neurotoxicité et néphrotoxicité induites." Paris 5, 2007. http://www.theses.fr/2007PA05P625.
Ifosfamide is a useful prodrug with CYP450 metabolisation associated to both antitumor activity and toxicities. Current evidence suggests that chloroacetaldehyde, a side-chain oxidation metabolite is responsible for neurotoxicity and nephrotoxicity. The aim of our research is to prevent chloroacetaldehyde formation. First, we designed and synthesized new enantioselective synthesized ifosfamide analogues i. E. C7,C9-dimethyl-ifosfamide. Two topics were investigated. First, metabolites determination of the IFO analogues was performed using HPLC-MS² after in vitro biotransformation by drug-induced rat liver microsomes. Secondly, the cytotoxicity of these prodrugs was evaluated. Finally, a mechanistic study using 31P-NMR kinetics allowed to estimate the alkylating activity of the modified mustards. Secondly, electrochemical biomimetic oxidation and preactivation of IFO were studied. This is a first step toward vectorisation of IFO
Zerbet, Mohamed. "Dérivés du benzamidazole à finalité thérapeutique : analogues du Hoechst 33258 et des NICE-NU (NitroImidazole ChloroEthyl NitrosoUrées)." Montpellier 2, 1990. http://www.theses.fr/1990MON20294.
Jourdan, Fabrice. "Synthèse, études physicochimique et pharmacologique d'inhibiteurs potentiels de la transcriptase inverse comprenant différents analogues de nucléosides cycliques et acycliques thiéno et dihydrothiénopyrimidiniques, différentes pyridin-2-ones et pyrido[3,2-ƒ]pyrollo[1,2-a]diazépines." Caen, 1996. http://www.theses.fr/1996CAEN4018.
Le, Roux Antoine. "Synthèse et activité biologique de dérivés et analogues de l’acide pulvinique pour une application en protection contre les rayonnements ionisants." Strasbourg, 2010. https://publication-theses.unistra.fr/public/theses_doctorat/2010/LE_ROUX_Antoine_2010.pdf.
The objective of this thesis was to synthesize and to evaluate the biological activity of hydrophilic derivatives and structural analogues of pulvinic acid, derived from norbadione A, a naturally occurring antioxidant found in mushrooms. This study aimed to develop new protective agents against ionizing radiations. First a scalable synthesis of a bis-lactone as a common intermediate was developed. It is based on the condensation and dehydratation of the anion of a protected tetronic acid on methyl pyruvate and subsequent selective demethylation in presence of magnesium bromide. This intermediate was then employed to prepare several hydrophilic derivatives by regioselective ring-opening of one lactone by functionalized amines. The second study was based on the creation of an in silico activity-predicting model allowed to highlights derivatives of 3-aryl-4-hydroxycoumarines as potential antioxidants. A synthesis pathway was used to prepare several derivatives to perform a structure-activity relationship study. All synthesized compounds were then tested in an in vitro assay, to investigate their radioprotective properties. Radiosensitive cells were exposed to the different compounds and irradiated, after several days their viability was assessed. Finally a third study was conducted to investigate the chelating activity of pulvinic acids towards 137Cs in order to develop new detoxifying agents
Brajeul, Solenn. "Produits naturels terpenoïdes dérivés d'acylphloroglucinols : travaux exploratoires en vue de la synthèse du xanthochymol et de ses analogues." Paris 11, 2005. http://www.theses.fr/2005PA112288.
Xanthochymol and guttiferones E and F are polyisoprenylated acylphloroglucins which inhibit the desassembly of miciotubules into tubulin. We have a project of total synthesis of these molecules using biogenesis hypothesis. Firstable, some studies about biomimetic synthesis have been done. Preparation of benzoylphloroglucinol has been studied. Then, prenylation under mild conditions using sulfonium salts have been studied. Finally some original electrophilic aromatic substitution have been developped using these salts. In a second part, the construction of the bicyclic moiety has been studied which has given several prenylated intermediairies. The synthesis of a polyprenylated β-ketoester has allowed the study of several methods to synthesize the bicycle. We observed great difficulties to get the bicycle due to the important steric hinderance mostly due to the gem-dimethyle. The synthesis of a diprenylated cyclohexanone should be usefull for the next studies. Finally the activity towards assembly or disassembly of microtubules has been studied for all the intermediary compounds
Mathé, Christophe. "Nouveaux analogues nucléosidiques à visée antivirale : synthèse et étude de dérivés du DRB et de nucléosides de configuration non naturelle L." Montpellier 2, 1994. http://www.theses.fr/1994MON20138.
Raboisson, Pierre. "Développement d'inhibiteurs de phosphodiestérase 4 et conception d'antagonistes purinergiques P2Y1 à partir de dérivés de l'adénine et de leurs analogues structuraux." Université Louis Pasteur (Strasbourg) (1971-2008), 2000. http://www.theses.fr/2000STR13243.
Vidil, Carole. "Synthèses et évaluations biologiques de phosphonates analogues du mannose 6-phosphate, substrats potentiels du récepteur mannose 6-phosphate." Montpellier 2, 1997. http://www.theses.fr/1997MON20247.
Montoir, David. "Synthèse de nouveaux analogues de la novobiocine, inhibiteurs potentiels de la Hsp90." Nantes, 2015. http://archive.bu.univ-nantes.fr/pollux/show.action?id=6c48ca52-acbc-4cf1-aaa9-deed157ff1bc.
The 90-kDa Heat shock protein (Hsp90) is an ATP-dependent chaperone known to play a crucial role in protein homeostasis. Hsp90 is directly involved in the conformational stability of « client proteins », many of which are associated with cancer cell survival. Thus, Hsp90 inhibition represents an attractive route for the development of new anticancer drugs. Novobiocin, an aminocoumarin antibiotic, was reported to inhibit Hsp90 targeting C-terminal domain, and showed anti-proliferative properties (IC50 = 700 μM in SKBr3, breast cancer cell line). The work presented here describes the synthesis of new analogs of novobiocin derived from 1,6- naphthyridin-2(1H)-one and 1,6-naphthyridin-4(1H)-one series. Newly synthesized compounds were evaluated against breast cancer cell lines for their antiproliferative activities and selected regarding their capacity to bind the mammalian Hsp90 and its fragments. The best candidates were subsequently tested by Western blot analysis to measure their ability to induce degradation of Hsp90 client proteins. In parallel a synthetic methodology involving palladium-catalyzed coupling reactions was developed to produce original 3,7-disubstituted 1,6-naphthyridin-2(1H)-ones
Kervio, Eric. "Synthons oxo alkyl-1,1-bisphophonates, intermédiaires dans l'obtention d'indoles 2 et/ou 3-alkyl-1',1'bisphophonates selon la réaction de cyclisation de Fischer : ciblage pharmacologique sur quelques analogues et conjugués de l'indométhacine." Brest, 1996. http://www.theses.fr/1996BRES2060.
Bouraiou, Abdelmalek. "Synthèse d'hétérocycles quinoléiques à visée thérapeutique et d'analogues structuraux de produits naturels." Rennes 1, 2009. http://www.theses.fr/2009REN1S126.
This manuscript describes the preparation of new quinolines derivatives associated to heterocycles eg. Aziridine, pyrrolidine or pyrrole and some structural analogues of flavanones, flavonols and tetrahydroquinolones. In this context, we have developed two methods. The first one consists on the generation of the N-metalated azométhine ylide from a -iminoesters in presence of LiBr in basic medium. The second one is based on the thermolysis of the N-alkylaziridine, which react with DMAD to offer N-alkylpyrroles and Delta-pyrrolines. In second part, we have reported the synthesis of new heterocyclic compounds with likely flavonoïd structures incorporating a quinoline unit, from the corresponding 2-hydroxy and 2-aminochalcones. These intermediates were utilized for the preparation of some new compounds that have a similar structure of flavanones, flavonols, 3-hydroxy-2,3-dihydroquinolin-(4)-ones. A new synthetic approach concerning the preparation of 1,2,3,4-tetrahydroquinolin-(4)-one derivatives through an intramolecular cyclization using a microwave irradiation have used with success
Dembele, Ousmane. "Design, synthèse et étude biologique de dérivés à structure imidazo[4,5-c]-1,6-naphtyridin-2(1H)-one et analogues structuraux à visée antiproliférative." Thesis, Nantes, 2018. http://www.theses.fr/2018NANT4004.
Protein kinase is a promising target for the treatment of many cancer pathologies. Enzymes effecting phosphorylation of proteins by transferring a phosphate group of ATP to a substrate protein. The latter then makes a conformational change that gives it new functions. If their action is performed on a phenolic amino acid, it will be called tyrosine kinase (TK) but if it is performed on a non-aromatic alcoholic amino acid, it will be called serine / threonine kinase (STK). The inhibition of its activity represents an important stake in the discovery of new anticancer molecules, thanks in particular to the knowledge of their structural organization. The original idea was to build on a marine-based structure to develop a drug discovery work. It was chosen from the structure of the grossularines A and B extracted from a marine tunicate (Dendrodoa grossularia) as a model since we had anteriority in the work on this type of structure. This made it possible to envisage the development of analogues and / or derivatives of these grossularins, with, in series pyridazinoindole, the identification of hits on PI3K or DYRK1A. Our work focuses on the synthesis of new original imidazo-naphthyridinone series molecules and structural analogues potentially inhibitory to kinases. The synthesized compounds were evaluated in parallel by the Roscoff Biological Station on a panel of kinases (HASPIN, CLK1, DYRK1A, CDK5, CDK9, and GSK3α/β and CK1)
Brunin, Thierry. "Conception et synthèse de dérivés de la camptothécine inhibiteurs potentiels de la topoisomérase I." Lille 2, 2004. http://www.theses.fr/2004LIL2S028.
Cancer is one of the most worrying and widespread disease in industrial countries. This disease is due to an anarchic proliferation of cells. Topoisomerase I and II are enzymes involved in cell division. Topoisomerase I is overexpressed in many types of cancer, so its inhibition is a pathway to fighting cancer. Camptothecin is a natural alcaloïd well known for many years for its antitumor properties. Its way of action is the inhibition of topoisomerase I. However, it shows too much toxicity to be used as a medicine. We have synthesised new derivatives of camptothecine modified at position 5
Saniere, Laurent. "Conception de petits peptides et peptidomimétiques dérivés de l'arginine comme modulateurs de la nociception : accès aux 4,5-dihydrotriazinones analogues rigides de dipeptides. Synthèse totale de l'enduracididine." Université Louis Pasteur (Strasbourg) (1971-2008), 2001. http://www.theses.fr/2001STR13154.
Grifon, Jean-François. "Analogues nucléosidiques inédits d'anomérie Bêta et d'énantiomérie non naturelle L : synthèse, propriétés antitumorales et antivirales de dérivés de la 5-fluorouracile et de la 5-fluorocytosine." Montpellier 2, 1998. http://www.theses.fr/1998MON20011.
Tian, Wen. "Etude phytochimique de Zanthoxylum unifoliolatum T. G. Hartley, ined. : synthèse et activité biologique de dérivés aminés et d'aza-analogues de la benzo[b]acronycine." Paris 5, 2004. http://www.theses.fr/2004PA05P617.
The first part of this work describes the chemical investigation of a new neocaledonian endemic species of Zanthoxylum, Zanthoxylum unifoliolatum. From the bark of Zanthoxylum unifoliolatum T. G. Hartley, ined, were isolated one coumarin and twelve alkaloids, two furoquinolines and ten benzo[c]phenanthridines. Two compounds of the benzo[c]phenanthridine series are new and were determined on the basic of the spectral data as the 6-methoxynoravicine and the 6-methoxynornitidine. The alkaloid acronycine ( 6-methoxy-3,3,12-trimethyl-3,12-dihydro-7H-pyrano-[2,3-c]acridin-7-one ), first isolated from Acronychia baueri Schott (Rutaceae), was subsequently shown to exhibit a broad spectrum of activity against numerous experimental tumors models. Neverthless, clinical trials gave only poor results, probably due to the moderate potency of this alkaloid. Further on, structural analogues with an additional aromatic ring linearly fused on the natural alkaloid skeleton were developed, and several cis-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one diesters proved even more potent. Among them, the cis-1,2-diacetate, currently under preclinical development under the code S 23906-1, and two series of amino derivatives have been prepared. Their in vitro cytotoxic activities have been evaluated against the murine L1210 leukemia cell line and the human colon tumor HT29, and are shown to exhibit cytotoxic activities comparable to those of their benzo[b]acronycine counterparts. One of the compounds is currently evaluating in vivo against the tumors colon 38 in mice
Gasnereau, Anne. "Conception, synthèse et évaluation pharmacologique d'analogues tétrahydroisoquinoléiniques et isoquinoléiniques de la mélatonine." Lille 1, 2005. https://pepite-depot.univ-lille.fr/LIBRE/Th_Num/2005/50376-2005-Gasnereau.pdf.
Desfougères-Fontaine, Aline. "Synthèse d'isoflavones prénylées dérivées de la génistéine." Université Joseph Fourier (Grenoble), 1997. http://www.theses.fr/1997GRE18002.
Minard, Corinne. "Doubles couplages de Suzuki-Miyaura sélectifs sur des dérivés dihalogénés symétriques - Application à la synthèse de la ningaline B et de ses analogues." Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00919884.
Ville, Alexia. "Métabolites secondaires et analogues hémisynthétiques en série vitaminique E : Obtention et évaluation du potentiel anti-inflammatoire." Thesis, Angers, 2018. http://www.theses.fr/2018ANGE0062.
Many studies highlighted the biological potential of tocotrienols (T3), a vitamin E subfamily, especially in the field of cardiovascular diseases and chronic inflammation. A phytochemical study, previously conducted at SONAS, led to the isolation and characterization of δ-amplexichromanol (δ-AC) as the main and original secondary metabolite from Garcinia amplexicaulis barks (dichloromethane extract) along with other oxidized T3 analogs such as δ-garcinoic acid (δ-GA). A pharmacophore based virtual screening of these derivatives against various anti-inflammatory targets showed that this class of T3 analogs could be considered as potential 5-LOX inhibitors. It was confirmed by in vitro assays when δ-AC and δ-GA were evaluated as inhibitors of purified 5-LOX, or in polymorphonuclear leukocytes. We then decided to carry on our study to further understand the original mode of action of these metabolites while optimizing the anti-inflammatory properties of the first hits. Such approach requires large amounts of tocotrienolic derivatives. However, usual natural sources of T3 provide complex mixtures involving particularly challenging purification processes. Thus, this work aim at designing efficient semisynthesis towards pharmacologically relevant T3 derivatives were developed from -GA, the main T3 derivative isolated from Garcinia kola nuts, a renewable and easily available vegetal source. Moreover, pharmacomodulation of the tocotrienolic backbone relied on preliminary docking studies and then required the development of various synthetic strategies to access original vitamin E analogs as potential 5-LOX inhibitors
Brossard, Dominique. "Synthèse de stéroïde-hétérocycles azotés analogues d'alcaloïdes stéroïdiques à activité anti-tumorale sur des lignées cancéreuses du colon et inhibiteurs d'enzymes impliquées dans les cancers hormono-dépendants." Caen, 2011. http://www.theses.fr/2011CAEN4073.
This work concerns the synthesis of heterocycle-steroid hybrids for promising therapeutic strategy. After a general literature review of heterocycle-steroid and nitrogen-containing heterocycle-steroid derivatives of cholic acids and androstene, syntheses of bile acid derivatives, androstene derivatives and cholesterol derivatives were carried out. The synthesized derivatives have been the subject of biological assays. On the one hand the activity studies of cholic acid derivatives on glioblastoma multiform, multiple myeloma and colonic carcinoma cell line, on the other hand the activity studies of cholic acid derivatives, abiraterone analogues and cholesterol derivatives as inhibitors of cytochrome P450 CYP 17 and CYP 19 (aromatase), therapeutic targets on hormone-dependent cancers. Promising results have been obtained, especially concerning cholic acid derivatives on colonic carcinoma cell lines, these derivatives acting by a pro-apoptotic mechanism. Abiraterone analogues showed good inhibition of cytochrome P450 CYP 17 and CYP 19 by interaction with the heme moiety of the enzyme. The experimental part of this document describes the procedures and physicochemical data of new synthesized compounds. Nearly 120 bibliographical references place this study in its chemical and biological context