Academic Journal
Synthesis and biological evaluation of new 3-(6-hydroxyindol-2-yl)-5-(Phenyl) pyridine or pyrazine V-Shaped molecules as kinase inhibitors and cytotoxic agents.
| العنوان: | Synthesis and biological evaluation of new 3-(6-hydroxyindol-2-yl)-5-(Phenyl) pyridine or pyrazine V-Shaped molecules as kinase inhibitors and cytotoxic agents. |
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| المؤلفون: | Kassis, Pamela, Brzeszcz, Joanna, Bénéteau, Valérie, Lozach, Olivier, Meijer, Laurent, Le Guével, Rémi, Guillouzo, Christiane, Lewiński, Krzysztof, Bourg, Stéphane, Colliandre, Lionel, Routier, Sylvain, Mérour, Jean-Yves |
| المساهمون: | Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS), Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff Roscoff (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Faculty of Chemistry, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 0223-5234. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2011 |
| المجموعة: | Université François-Rabelais de Tours: HAL |
| مصطلحات موضوعية: | MESH: Antineoplastic Agents, MESH: Catalysis, MESH: Indoles, MESH: Microwaves, MESH: Models, Molecular, MESH: Molecular Conformation, MESH: Palladium, MESH: Protein Kinase Inhibitors, MESH: Protein Kinases, MESH: Pyrazines, MESH: Pyridines, MESH: Structure-Activity Relationship, MESH: Cell Line, Tumor, MESH: Chemistry Techniques, Synthetic, MESH: Humans, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry |
| الوصف: | International audience ; We here report the synthesis and biological evaluation of new 3-[(2-indolyl)]-5-phenyl-3,5-pyridine, 3-[(2-indolyl)]-5-phenyl-2,4-pyridine and 3-[(2-indolyl)]-5-phenyl-2,6-pyrazine derivatives designed as potential CDK inhibitors. Indoles and phenyls were used to generate several substitutions of the pyridine and pyrazine rings. The synthesis included Stille or Suzuki type reactions, which were carried out on the 3,5-dibromopyridine, 2,4-dichloropyridine and 2,6-dichloro-1-4-pyrazine moieties. Cell effects of the V-shaped family were in the micromolar range. Kinase assays were conducted and showed that compound 11 inhibited CDK5 with an inhibitory concentration of 160 nM with a moderate selectivity over GSK3 compared to the reference C which exhibited a slightly lower activity on CDK5 (1.5 μM). Compound 11 was also found to be the most potent compound in the series and was identified as a new lead for DYRK1A inhibitor discovery (IC(50) = 60 nM). Docking studies were carried out in order to investigate the inhibition of DYRK1A. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/21944287; hal-00720615; https://hal.science/hal-00720615; PUBMED: 21944287 |
| DOI: | 10.1016/j.ejmech.2011.08.048 |
| الاتاحة: | https://hal.science/hal-00720615 https://doi.org/10.1016/j.ejmech.2011.08.048 |
| رقم الانضمام: | edsbas.2C7432F6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.ejmech.2011.08.048 |
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