Reproduction de : Thèse de doctorat : Chimie des polymères : Université Cergy-Pontoise : 2008. / Titre provenant de l'écran titre. Références bibliogr. en fins de chapitres.

Thesis (M.S.)--West Virginia University, 2004. / Title from document title page. Document formatted into pages; contains ix, 72 p. : ill. Includes abstract. Includes bibliographical references (p. 49-52).

L’ellipticine, alcaloïde tétracyclique naturel au squelette 6H-pyrido[4,3-b]carbazole, et certains de ses dérivés possèdent des propriétés antitumorales. L’objectif de ce travail a été, d’une part de trouver une méthode de synthèse de deux types d’intermédiaires précis non décrits à notre connaissance (dérivés du carbazole et de la pyridine), puis de synthétiser des analogues d’ellipticine possédant un cycle saturé supplémentaire, ces modifications structurales pouvant être intéressantes du point de vue de l’activité biologique. Initialement envisagée à partir de dérivés du furane par ouverture du cycle furanique en milieu acide, les dérivés carbazoliques 10-méthyl-1,10-dihydrocyclopenta[a]carbazol-3(2H)-one, 1,2,3,11-tétrahydro-4H-benzo[a]carbazol-4-one, 2,3,4,11-tétrahydro-1H-benzo[a]carbazol-1-one, et 11-méthyl-1,2,3,11-tétrahydro-4H-benzo[a]carbazol-4-one ont finalement été obtenus grâce à la synthèse indolique de Fischer, puis réaction de Friedel-Crafts pour la première molécule et réduction par les métaux dissous, oxydation par la DDQ pour les trois suivantes. Un des dérivés carbazoliques synthétisés nous a fourni par la méthode d’Eloy et Deryckere des analogues de l’ellipticine contenant un cycle saturé supplémentaire à six chaînons, molécules au squelette 1,2,3,12-tétrahydroisoquino[5,4-ab]carbazole, le produit final possédant une chaîne polyaminée, considérée comme utile pour obtenir une activité biologique significative. D’autres systèmes hétérocycliques ont été synthétisés à partir des intermédiaires carbazoliques, notamment des nouveaux dihydrocarbazolocarbazoles / Ellipticine, a tetracyclic natural alkaloid with the 6H-pyrido[4,3-b]carbazole skeleton and some of its derivatives display antitumoral properties. The aim of this work was firstly to find a general method to synthesize two types of intermediates not described in the literature to our knowledge (carbazole and pyridine derivatives), and then to synthesize some ellipticine analogs, which contain an additional saturated cycle, these structural modifications could be interesting regarding to biological activity. The synthesis was initially thought starting from furan derivatives, and opening of the ring under acidic conditions. 10-Methyl-1,10-dihydrocyclopenta[a]carbazol-3(2H)-one, 1,2,3,11-tetrahydro-4H-benzo[a]carbazol-4-one, 2,3,4,11-tetrahydro-1H-benzo[a]carbazol-1-one, and 11-methyl-1,2,3,11-tetrahydro-4H-benzo[a]carbazol-4-one were eventually obtained by Fischer indole synthesis, followed by Friedel-Crafts reaction for the first product and dissolved metal reduction, DDQ oxidation for the three other molecules. Second hoped intermediates, for instance 5,6,7,8-tetrahydroisoquinoline derivative 3-chloro-7,8-dihydro-6H-isoquinolin-5-one, were not obtained. One of the carbazolic derivatives afforded by the Eloy and Deryckere method ellipticine analogs containing an additional 6-member saturated ring, molecule having a 1,2,3,12-tetrahydroisoquino[5,4-ab]carbazole scaffold. Final product of this synthesis has a polyaminated chain, needed to find a biological activity. Other heterocyclic systems were synthesized from the carbazolic intermediates, like some new dihydrocarbazolocarbazoles

Solid state lighting industry is booming in recent years because of the green energy requirement. Therefore, phosphorescent OLEDs using phosphorescent emitters doped into charge-transporting hosts as emissive layers (EMLs) have attracted extensive interest due to their highly efficient emission compared to conventional fluorescent OLEDs, through radiative harvesting of both electro-generated singlet and triplet excitons. To achieve better charge balance and device performance, many researchers focus on developing new phosphorescent host materials with bipolar charge transporting property. In this work, we successfully designed and synthesized a host material CzppT containing hole-transporting carbazole and electron-transporting pyridine and investigated the physical properties. With a high triplet energy, CzppT is considered a promising universal host material and has been applied to phosphorescent OLEDs of blue/white colors. Blue/white OLEDs based on CzppT as host and Firpic/Ir(piq)2(acac) as dopant materials show maximum external quantum efficiencies (11.0% for blue, 11.32% for white) and CIE coordinates [(0.18,0.41)for blue, (0.32,0.36) for white)]. The results indicate that the bipolar host CzppT with high triplet energy has potential in manufacturing blue and white OLEDs for display or lighting applications.

Marine natural products which contain a £]- carboline skeleton are widely distributed in marine invertebrates. The discovery of natural £]- carboline metabolites as potent antitumor and antival agents has stimulated a great interest on the synthetic and pharmatological studies of£]- carboline derivatives. Herein, the preparation, charactrization and biolgical evaluation of 1-substituted 1,2,3,4-tetrahydro-£]- carboline and 3,4-dihydro-£]- carboline derivatives are reported. A facile synthetic method by the application of Pictet-Sengler reaction and DDQ oxidation allowed the preparation of compounds 63-72. Compounds 63-67 were synthesized from tryptamine and N-substituted-3-carbazole carboxaldehyde via Pictet-Spengler cyclization. Subsequent oxidation of compounds 63-67 by DDQ furnished compounds 68-72. The structures of compounds 63-67 were determined by several spectroscopic methods. A series of 1-substituted-1,2,3,4-tetrahydro-£]- carboline (63-67) and 3,4-dihydro-£]- carboline derivatives (68-72) have been evaluated to possess cytotoxicity against human tumor cells including KB16, DLD and NCI cell lines. On the other hand, chromatographic separation of acetone extract of Formosan grogonian coral Isis hippuris (collected in Gree island) has led to the isolation of four marine steroids namely hippurin-1 (74), 22-epi-hippurin-1 (80), 2-deacetylhippurin-1 (82) and 2-deacetyl-22-epi-hippurin-1 (83), as well as a new compound 4-hydroxy-5-(p-hydroxy phenyl)-pentane-2, 5-dione (86). The structures of all above compounds were established on the basis of spectral analysis. Biological studies revealed that compounds 74, 80, 82, 83 exhibited potent cytotoxicity against NUGC tumor cells, but compound 86 was inactive.

Reproduction de : Thèse doctorat : Chimie des polymères : Université de Cergy-Pontoise : 2005. / Titre provenant de l'écran titre. Bibliogr. p.155-158.

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Thesis (M.S.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains ix, 74 p. : ill. Includes abstract. Includes bibliographical references (p. 58-60).

Alzheimer's disease is the most common neurodegenerative disease in the elderly. Senile plaques and nerve cells in the fiber entanglement [neurofibrillary tangle (NFT)] are the significant pathological features. Currently, clinical drugs cannot effectively treat AD and reverse its pathogenesis. Therefore, it is of great importance to research and development of new AD therapy drugs. Carbazole-based cyanine is a type of synthetic small molecule compound that shares a common base with different functional groups; for example, SLOH, SLM, and SLCOOH. They exhibited selective binding to Aβ peptides and showed strong inhibition of Aβ peptide aggregation. It was found that one of the cyanines, SLOH, could significantly improve the cognitive ability of 3× Tg-AD mice treated for 40 days from the age of 4 months. In vivo, SLOH reduced Aβ levels and decreased hyperphosphorylation of tau both in the hippocampus and cortex by downregulating the activity of Akt/GSK3β and protein phosphatase 2A, SLOH can also activate the calcium pathway through activating CAMKII and cAMP-response element-binding (CREB). SLM significantly improved cognitive deficits in AD mice both in AD mice aged 4 months and 8 months. Both oligomeric Aβ and phosphorylated tau were decreased, and this was due to the activation of autophagic flux. The other cyanine compound SLCOOH also exhibited significant improvement in the cognitive ability of 4-month 3× Tg-AD mice after two months of treatment. There was significantly reduced Aβ deposition, decreased total tau, and reduced tau hyperphosphorylation by inhibiting the activities of glycogen synthase kinase-3β in 4-month 3× Tg-AD mice. SLCOOH treatment cleared Aβ and tau by upregulating the autophagy pathway, which inhibited the activity of mTOR/p70S6K. Moreover, SLCOOH structurally restored synapses and spines and regulated the Ca2+/CaMKII/CREB signaling pathway, leading to enhanced synaptic plasticity and cognitive ability in AD mice. Furthermore, we found SLCOOH ameliorated synaptic deficits by downregulating N-methyl-D-aspartate receptors (NMDAR), thereby modulating intercellular calcium ion (Ca2+) loading and upregulating neuronal calcium dependent signaling. Thus, our results demonstrated that these three carbazole-based cyanines mitigated cognitive decline by targeting Aβ and tau pathology in 3× Tg-AD mice. Those data strongly support that these three carbazole-based cyanines as a potent therapy for AD.

Alzheimer's disease is the most common neurodegenerative disease in the elderly. Senile plaques and nerve cells in the fiber entanglement [neurofibrillary tangle (NFT)] are the significant pathological features. Currently, clinical drugs cannot effectively treat AD and reverse its pathogenesis. Therefore, it is of great importance to research and development of new AD therapy drugs. Carbazole-based cyanine is a type of synthetic small molecule compound that shares a common base with different functional groups; for example, SLOH, SLM, and SLCOOH. They exhibited selective binding to Aβ peptides and showed strong inhibition of Aβ peptide aggregation. It was found that one of the cyanines, SLOH, could significantly improve the cognitive ability of 3× Tg-AD mice treated for 40 days from the age of 4 months. In vivo, SLOH reduced Aβ levels and decreased hyperphosphorylation of tau both in the hippocampus and cortex by downregulating the activity of Akt/GSK3β and protein phosphatase 2A, SLOH can also activate the calcium pathway through activating CAMKII and cAMP-response element-binding (CREB). SLM significantly improved cognitive deficits in AD mice both in AD mice aged 4 months and 8 months. Both oligomeric Aβ and phosphorylated tau were decreased, and this was due to the activation of autophagic flux. The other cyanine compound SLCOOH also exhibited significant improvement in the cognitive ability of 4-month 3× Tg-AD mice after two months of treatment. There was significantly reduced Aβ deposition, decreased total tau, and reduced tau hyperphosphorylation by inhibiting the activities of glycogen synthase kinase-3β in 4-month 3× Tg-AD mice. SLCOOH treatment cleared Aβ and tau by upregulating the autophagy pathway, which inhibited the activity of mTOR/p70S6K. Moreover, SLCOOH structurally restored synapses and spines and regulated the Ca2+/CaMKII/CREB signaling pathway, leading to enhanced synaptic plasticity and cognitive ability in AD mice. Furthermore, we found SLCOOH ameliorated synaptic deficits by downregulating N-methyl-D-aspartate receptors (NMDAR), thereby modulating intercellular calcium ion (Ca2+) loading and upregulating neuronal calcium dependent signaling. Thus, our results demonstrated that these three carbazole-based cyanines mitigated cognitive decline by targeting Aβ and tau pathology in 3× Tg-AD mice. Those data strongly support that these three carbazole-based cyanines as a potent therapy for AD.