title: Design, synthesis, and molecular modelling of pyridazinone and phthalazinone derivatives as protein kinases inhibitors.
abstract: The design and synthesis of pyridazinone and phthalazinone derivatives are described. Newly synthesized compounds were tested on a panel of four kinases in order to evaluate their activity and potential selectivity. In addition, the promising compounds were tested on four cancer cell lines to examine cytotoxic effects. The compounds inhibited DYRK1A and GSK3 with different activity. SAR analysis and docking calculations were carried out to aid in the interpretation of the results. Taken together, our findings suggest that pyridazinone and phthalazinone scaffolds are interesting starting points for design of potent GSK3 and DYRK1A inhibitors.
authors: Laboratoire d'innovation thérapeutique, UMR 7200, Faculté de Pharmacie, Université de Strasbourg, 74-route du Rhin, BP 60024, 67401 ILLKIRCH Cedex, France. alfath_tours@yahoo.com
authors: Mohamed
authors: M
authors: Elagawany
authors: Mohamed A
authors: MA
authors: Ibrahim
authors: Hany Emary
authors: HE
authors: Ali Ahmed
authors: A Sh
authors: ASh
authors: El-Etrawy
authors: Adel
authors: A
authors: Ghiaty
authors: Zakaria K
authors: ZK
authors: Abdel-Samii
authors: Said A
authors: SA
authors: El-Feky
authors: Jürgen
authors: J
authors: Bajorath
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047389:Casein Kinase I / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010793:Phthalazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000097603:Dyrk Kinases
chemical_list: D000970:Antineoplastic Agents; D047389:Casein Kinase I; D051360:Cyclin-Dependent Kinase 5; D038362:Glycogen Synthase Kinase 3; D010793:Phthalazines; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011724:Pyridazines; D000097603:Dyrk Kinases