Dissertation/ Thesis
Synthesis and evaluation of new CXCR1-2 receptor antagonists to target both angiogenesis and inflammation in oncology ; Synthèse et évaluation de nouveaux antagonistes des récepteurs CXCR1-2 pour cibler conjointement l’angiogenèse et l’inflammation dans les pathologies cancéreuses
| العنوان: | Synthesis and evaluation of new CXCR1-2 receptor antagonists to target both angiogenesis and inflammation in oncology ; Synthèse et évaluation de nouveaux antagonistes des récepteurs CXCR1-2 pour cibler conjointement l’angiogenèse et l’inflammation dans les pathologies cancéreuses |
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| المؤلفون: | Mateo, Lou |
| المساهمون: | Institut de Chimie de Nice (ICN), Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA), Université Côte d'Azur, Rachid Benhida, Luc Demange |
| المصدر: | https://theses.hal.science/tel-04213465 ; Chimie thérapeutique. Université Côte d'Azur, 2021. Français. ⟨NNT : 2021COAZ4006⟩. |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2021 |
| المجموعة: | HAL Université Côte d'Azur |
| مصطلحات موضوعية: | ELR+-CXCL cytokine, CXCR1 and CXCR2 inhibitors, Angiogenesis, Inflammation, Benzothiazinones, Cytokines CXCL-ELR+, Angiogenèse, Inhibiteurs de CXCR1 et CXCR2, 2-aminobenzothiazinones, [CHIM.THER]Chemical Sciences/Medicinal Chemistry |
| الوصف: | Cancer is one of the main causes of death in the world. Angiogenesis and inflammation represent two essential hallmarks in the development and progression of tumors and are essential for the survival of the cancer cells. Better knowledge of cellular mechanisms has enabled the development of targeted anti-angiogenic therapies. However, the emergence of resistance constitutes the main limitation of these current anti-angiogenics targeted therapies, as you may know the anti-VEGF therapies. But in parallel to the VEGF pathway, another crucial pro-angiogenic and pro-inflammatory axis in cancers is required: the CXCL-ELR+/CXCR pathway, particularly in metastatic kidney cancer. The aim of this work was to develop original small organic molecules able to inhibit the ligand/receptor interaction (CXCL-ELR+ / CXCR1-2) in order to have both anti-inflammatory and anti-angiogenic activities. The 2-aminobenzothiazinone pattern was chosen for the preparation of 3 new classes of inhibitors. Divergent synthesis strategies were used to obtain the members of families 1 & 2, although the conditions have been adapted according to the reactivity of each substrate. The last family of molecules was prepared according to a linear synthesis. However, this latter strategy displayed some limitations during the cyclisation step. Thereafter, biological evaluations revealed a promising compound exhibiting an IC50 of 0.6 μM on the 786-O cell line compared with our reference molecule (IC50 = 2 μM). Other result highlighted that this compound also exerted an inhibition of the chemotaxis of cells expressing CXCR1-2 receptors. Further studies on zebrafish are planned with this compound in order to study its ability to interfere with the angiogenesis phenomenon in vivo. ; L’angiogenèse et l’inflammation sont deux acteurs primordiaux dans le développement et la progression de nombreux cancers. Une meilleure connaissance des mécanismes cellulaires a permis l’essor des thérapies ciblées anti-angiogéniques. L’intérêt de ces thérapies ciblées ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | French |
| Relation: | NNT: 2021COAZ4006; tel-04213465; https://theses.hal.science/tel-04213465; https://theses.hal.science/tel-04213465/document; https://theses.hal.science/tel-04213465/file/2021COAZ4006.pdf |
| الاتاحة: | https://theses.hal.science/tel-04213465 https://theses.hal.science/tel-04213465/document https://theses.hal.science/tel-04213465/file/2021COAZ4006.pdf |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.87C63DBB |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |