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Pyrrole

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Three enzymes control tryptophan to kynurenine metabolism: indoleamine 2, 3-dioxygenase 1 (IDO1), indoleamine 2, 3-dioxygenase 2 (IDO2) and tryptophan 2, 3-dioxygenase (TDO). Among them, IDO1 and TDO are overexpressed in tumor tissues and create an immunocompromised environment. The tryptophan depletion induced by these enzymes causes the dysfunction and /or apoptosis of effector T cells by activation of GCN2 which leads to cell cycle arrest, by inhibition of mTOR leading to autophagy, and by inhibition of PKC-θ leading to energy. As for the accumulation of kynurénine weakens the response of NK. All of this contributes to the creation of an immunosuppressed and pro-inflammatory environment. Therefore, IDOs and TDO, but several molecules are in preclinical phase. This master thesis describes in details the characteristics of IDOs and TDO, their catalytic mechanisms, and their immune-system escape mechanisms. It lists the small molecules that inhibit IDO1 and the dual inhibitors that are currently in clinical trials and in preclinical phase, which will give an idea of whether a new anti-cancer drug is coming or not. L'indoleamine 2,3-dioxygénase 1 (IDOI), l’indoleamine 2,3-dioxygénase 2 (ID02), et la tryptophane 2,3-dioxygénase (TDO) sont trois enzymes responsables du catabolisme du tryptophane en kynurénine. Parmi elles, IDO1 et TDO sont surexprimées dans les tissus tumoraux et créent un environnement immunodéprimé. La déplétion en tryptophane induite par ces enzymes entraine la dysfonction et/ou l'apoptose des lymphocytes T effecteurs par activation de GCN2 qui mène à l'arrêt du cycle cellulaire, par l’inhibition de mTOR qui mène à l'autophagie, et par l'inhibition de la PKC-θ qui mène à l'anergie. Quant à l'accumulation de kynurénine, elle entraine l'induction de lymphocytes T régulateurs immunosupresseurs par une activation de AhR. De plus, la kynurénine affaiblit la réponse des NK. Tout cela participe à la création d'un environnement immunodéprimé et pro-inflammatoire. IDOs et TDO sont donc des enzymes cibles intéressantes. Les inhiber permettrait de posséder une arme de plus pour se battre contre les divers types de cancer. Mais est-ce possible et réalisable de développer un inhibiteur mixte d'IDOs et TDO ? Plusieurs petites molécules ciblant IDO1 sont actuellement en essais cliniques, certaines ont déjà atteint la phase 3. Par ailleurs, seule une molécule est présentée comme un inhibiteur mixte d'IDO1 et TDO, mais plusieurs sont en phase préclinique. Ce mémoire décrit en détails les caractéristiques d'IDOs et TDO, leur mécanisme catalytique et les mécanismes menant à l'échappement au système immunitaire. Il établit une liste des petites molécules inhibitrices d'IDO1 et des inhibiteurs mixtes actuellement en essais cliniques et en phase préclinique, qui permettra de donner une idée sur la possibilité d'obtenir réellement ou non un nouveau médicament anti­ cancéreux.

Immunotherapy --- Indoleamine-Pyrrole 2,3,-Dioxygenase --- Tryptophan Oxygenase

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Indoles continue to be of great interest to the pharmaceutical industry and at the current time several thousand specific new derivatives are reported annually. Research has been driven by the wide range of indole derivatives which occur in nature and through the biological activity of many indole derivatives, of both natural and synthetic origin.This book provides a systematic guide to the most useful and important reactions in the field for both synthesis and synthetic modification of the indole ring. While including the most recently developed and promising methods, it also updates informat

Indoles. --- 547.75 --- #WSCH:LOSH --- 547.75 Condensed systems with one pyrrole ring. Indole. Skatole. Indoxyl. Tryptophane. Indigo blue. Indigo white. Indigo carmine --- Condensed systems with one pyrrole ring. Indole. Skatole. Indoxyl. Tryptophane. Indigo blue. Indigo white. Indigo carmine --- Indole --- Synthesis. --- Organic compounds --- Chemistry, Organic --- Chemistry, Synthetic organic --- Organic synthesis (Chemistry) --- Synthetic organic chemistry --- Synthesis

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In the landscape of the design of carbon nanomaterials, the fine-tuning of their functionalities and physico-chemical properties has increased their potential for therapeutic, diagnostic, and biosensing applications. In this editorial, we will provide a brief overview of the contents of this Special Issue. In particular, nanoplatforms originating from the synergistic combination of carbon-based nanomaterials (i.e., nanotubes, graphene, graphene oxide, carbon quantum dots, nanodiamond, etc.) with various functional molecules such as drugs, natural compounds, biomolecules, polymers, metal nanoparticles, and macrocycles that have useful applications in drug delivery, multi-targeted therapies, theranostic as well as scaffolds in tissue engineering, and as sensing materials have been selected for publication as Articles or Mini Reviews. The variety of applications covered by the nine articles published in this Special Issue of Nanomaterials are proof of the growing attention that the use of carbon nanomaterials in the biomedical/pharmaceutical field has received in recent years. We hope that readers find the contents of this Special Issue useful for their research, which is aimed to advance carbon nanomaterials from the laboratory to clinical nanomedicine.

graphene oxide --- covalent functionalization --- cortical membranes --- calcium phosphate deposition --- graphene/gold nanocomposite --- SERS --- Dopamine --- Rhodamine 6G --- nanodiamond --- tritium --- biodistribution --- Ewing sarcoma --- drug delivery --- siRNA --- nanomedicine --- porphyrin --- J-aggregates --- carbon nanotubes --- nanohybrids --- graphene --- liquid biopsy --- circulating tumor cells --- exosomes --- circulating nucleic acids --- COVID-19 --- pyrrole --- cancer --- doxorubicin --- drug delivery systems --- nanoparticles --- carbon dots --- platelet aggregation --- arterial thrombosis --- signaling molecules --- bleeding disorder --- cytotoxicity --- carbon nanomaterials --- camptothecin --- Caco-2 --- MCF-7 --- NanoHy-GPS --- antibacterial nanosystems --- one-pot microwave-assisted reaction --- silver nanoparticles --- polyvinyl alcohol --- n/a

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Nitro chemistry plays an important role in organic synthesis to construct new frameworks. This is due to the diverse properties of the nitro group. The strong electron-withdrawing ability of the nitro group reduces the electron density of the scaffold, facilitating reactions with nucleophiles or electron transfer. In addition, the -hydrogen of the nitro group is highly acidic, giving a stable anion, which facilitates reactions with both electrophilic and nucleophilic reagents. In addition, the nitro group also serves as a good leaving group, which facilitates transformation to a wide variety of functional groups. Despite the substantial contributions of many researchers, nitro chemistry is still an exciting and challenging research area. This book brings together recent original research and review articles contributed by an international team of leading experts and pioneers in organic synthesis using nitro groups. It is sure to provide useful information and promising insights for researchers.

Research & information: general --- nitro --- pyridone --- 1-methyl-2-quinolone --- cycloaddition --- direct functionalization --- perylenediimide --- nitro group --- organic materials --- Phenacylation of beta-nitropyridin-2-ones --- 8-nitro-5-RO-indolizines --- oxazole-pyrrole ring transformation --- conjugate addition --- dihydrofuran --- 1,3-dicarbonyl compound --- enolate --- isoxazoline N-oxide --- nitroketone --- nitronate --- nucleophilic substitution --- nitropyridines --- isoxazolo[4,3-b]pyridines --- 1,4-dihydropyridines --- nucleophilic addition --- Diels-Alder reaction --- dearomatization --- hexapyrrolohexaazacoronene --- nitration --- SNAr substitution --- ICT character --- aromaticity --- C–H functionalization --- total synthesis --- pyrrolidines --- anchimeric assistance --- epimerization --- PDE4 inhibitors --- 1,3-Dipole --- electron-withdrawing ability --- electrophilicity --- nucleophilicity