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- Title
Design and Microwave Synthesis of New (5 Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5 Z) 2-Amino-5-arylidene-1,3-thiazol-4(5 H)-one as New Inhibitors of Protein Kinase DYRK1A.
- Authors
Bourahla, Khadidja; Guihéneuf, Solène; Limanton, Emmanuelle; Paquin, Ludovic; Le Guével, Rémy; Charlier, Thierry; Rahmouni, Mustapha; Durieu, Emilie; Lozach, Olivier; Carreaux, François; Meijer, Laurent; Bazureau, Jean-Pierre
- Abstract
Here, we report on the synthesis of libraries of new 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones 3 (twenty-two compounds) and new 2-amino-5-arylidene-1,3-thiazol-4(5H)-ones 5 (twenty-four compounds) with stereo controlled Z-geometry under microwave irradiation. The 46 designed final compounds were tested in order to determine their activity against four representative protein kinases (DYR1A, CK1, CDK5/p25, and GSK3α/β). Among these 1,3-thiazolidin-4-ones, the molecules (5Z) 5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one 3e (IC50 0.028 μM) and (5Z)-5-benzo[1,3]dioxol-5-ylmethylene-2-(pyridin-2-yl)amino-1,3-thiazol-4(5H)-one 5s (IC50 0.033 μM) were identified as lead compounds and as new nanomolar DYRK1A inhibitors. Some of these compounds in the two libraries have been also evaluated for their in vitro inhibition of cell proliferation (Huh7 D12, Caco2, MDA-MB 231, HCT 116, PC3, and NCI-H2 tumor cell lines). These results will enable us to use the 1,3-thiazolidin-4-one core as pharmacophores to develop potent treatment for neurological or oncological disorders in which DYRK1A is fully involved.
- Subjects
PROTEIN kinase inhibitors; MICROWAVES; PROTEIN kinases; CELL lines; CELL proliferation; MICROWAVE spectroscopy
- Publication
Pharmaceuticals (14248247), 2021, Vol 14, Issue 11, p1086
- ISSN
1424-8247
- Publication type
Article
- DOI
10.3390/ph14111086