Design,synthesis, and molecular modelling of pyridazinone and phthalazinone derivatives as protein kinases inhibitors |
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| Authors: | Mohamed Elagawany Mohamed A. Ibrahim Hany Emary Ali Ahmed A.Sh. El-Etrawy Adel Ghiaty Zakaria K. Abdel-Samii Said A. El-Feky Jürgen Bajorath |
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| Affiliation: | 1. Laboratoire d’innovation thérapeutique, UMR 7200, Faculté de Pharmacie, Université de Strasbourg, 74-route du Rhin, BP 60024, 67401 ILLKIRCH Cedex, France;2. Organic Chemistry Department, College of Pharmacy, Misr University for Science and Technology, Al-Motamayez District, 6th of the October, PO Box 77, Egypt;3. Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt;4. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig-44519, Egypt;5. Pharmacognosy and Pharmaceutical Chemistry Department, Pharmacy College, Taibah University, Al-Madinaha Al-Munawaraha, Saudi Arabia;6. Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, D-53113 Bonn, Germany |
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| 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. |
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