Design and Microwave Synthesis of New (5<i>Z</i>) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5<i>Z</i>) 2-Amino-5-arylidene-1,3-thiazol-4(5<i>H</i>)-one as New Inhibitors of Protein Kinase DYRK1A
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(5<i>H</i>)-ones 5 (twenty-four compounds) with stereo controlled <i>Z</i>-geometry under microwave irradiation....
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MDPI AG
2021
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oai:doaj.org-article:f485bcb043cf40dc8c7981c1ef774c972021-11-25T18:39:13ZDesign and Microwave Synthesis of New (5<i>Z</i>) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5<i>Z</i>) 2-Amino-5-arylidene-1,3-thiazol-4(5<i>H</i>)-one as New Inhibitors of Protein Kinase DYRK1A10.3390/ph141110861424-8247https://doaj.org/article/f485bcb043cf40dc8c7981c1ef774c972021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1086https://doaj.org/toc/1424-8247Here, 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(5<i>H</i>)-ones 5 (twenty-four compounds) with stereo controlled <i>Z</i>-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 (5<i>Z</i>) 5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one 3e (IC<sub>50</sub> 0.028 μM) and (5<i>Z</i>)-5-benzo[1,3]dioxol-5-ylmethylene-2-(pyridin-2-yl)amino-1,3-thiazol-4(5<i>H</i>)-one 5s (IC<sub>50</sub> 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.Khadidja BourahlaSolène GuihéneufEmmanuelle LimantonLudovic PaquinRémy Le GuévelThierry CharlierMustapha RahmouniEmilie DurieuOlivier LozachFrançois CarreauxLaurent MeijerJean-Pierre BazureauMDPI AGarticlemicrowaveKnoevenagel condensationsulphur/nitrogen displacement1,3-thiazolidin-4-oneinhibitionprotein kinaseMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1086, p 1086 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
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| topic |
microwave Knoevenagel condensation sulphur/nitrogen displacement 1,3-thiazolidin-4-one inhibition protein kinase Medicine R Pharmacy and materia medica RS1-441 |
| spellingShingle |
microwave Knoevenagel condensation sulphur/nitrogen displacement 1,3-thiazolidin-4-one inhibition protein kinase Medicine R Pharmacy and materia medica RS1-441 Khadidja Bourahla Solène Guihéneuf Emmanuelle Limanton Ludovic Paquin Rémy Le Guével Thierry Charlier Mustapha Rahmouni Emilie Durieu Olivier Lozach François Carreaux Laurent Meijer Jean-Pierre Bazureau Design and Microwave Synthesis of New (5<i>Z</i>) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5<i>Z</i>) 2-Amino-5-arylidene-1,3-thiazol-4(5<i>H</i>)-one as New Inhibitors of Protein Kinase DYRK1A |
| description |
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(5<i>H</i>)-ones 5 (twenty-four compounds) with stereo controlled <i>Z</i>-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 (5<i>Z</i>) 5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one 3e (IC<sub>50</sub> 0.028 μM) and (5<i>Z</i>)-5-benzo[1,3]dioxol-5-ylmethylene-2-(pyridin-2-yl)amino-1,3-thiazol-4(5<i>H</i>)-one 5s (IC<sub>50</sub> 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. |
| format |
article |
| author |
Khadidja Bourahla Solène Guihéneuf Emmanuelle Limanton Ludovic Paquin Rémy Le Guével Thierry Charlier Mustapha Rahmouni Emilie Durieu Olivier Lozach François Carreaux Laurent Meijer Jean-Pierre Bazureau |
| author_facet |
Khadidja Bourahla Solène Guihéneuf Emmanuelle Limanton Ludovic Paquin Rémy Le Guével Thierry Charlier Mustapha Rahmouni Emilie Durieu Olivier Lozach François Carreaux Laurent Meijer Jean-Pierre Bazureau |
| author_sort |
Khadidja Bourahla |
| title |
Design and Microwave Synthesis of New (5<i>Z</i>) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5<i>Z</i>) 2-Amino-5-arylidene-1,3-thiazol-4(5<i>H</i>)-one as New Inhibitors of Protein Kinase DYRK1A |
| title_short |
Design and Microwave Synthesis of New (5<i>Z</i>) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5<i>Z</i>) 2-Amino-5-arylidene-1,3-thiazol-4(5<i>H</i>)-one as New Inhibitors of Protein Kinase DYRK1A |
| title_full |
Design and Microwave Synthesis of New (5<i>Z</i>) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5<i>Z</i>) 2-Amino-5-arylidene-1,3-thiazol-4(5<i>H</i>)-one as New Inhibitors of Protein Kinase DYRK1A |
| title_fullStr |
Design and Microwave Synthesis of New (5<i>Z</i>) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5<i>Z</i>) 2-Amino-5-arylidene-1,3-thiazol-4(5<i>H</i>)-one as New Inhibitors of Protein Kinase DYRK1A |
| title_full_unstemmed |
Design and Microwave Synthesis of New (5<i>Z</i>) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5<i>Z</i>) 2-Amino-5-arylidene-1,3-thiazol-4(5<i>H</i>)-one as New Inhibitors of Protein Kinase DYRK1A |
| title_sort |
design and microwave synthesis of new (5<i>z</i>) 5-arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5<i>z</i>) 2-amino-5-arylidene-1,3-thiazol-4(5<i>h</i>)-one as new inhibitors of protein kinase dyrk1a |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/f485bcb043cf40dc8c7981c1ef774c97 |
| work_keys_str_mv |
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