Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A

Institut des Sciences Chimiques de Rennes ISCR UMR CNRS 6226, Université de Rennes 1, Bât. 10A, Campus de Beaulieu, CS 74205, 263 Avenue du Général Leclerc, CEDEX, 35042 Rennes, France

S2Wave Platform, ScanMAT UMS 2001 CNRS, Université de Rennes 1, Bât. 10A, Campus de Beaulieu, CS 74205, 263 Avenue du Général Leclerc, CEDEX, 35042 Rennes, France

ImPACcell Platform, SFR Biosit, Université de Rennes 1, Bât. 8, Campus Villejean, 2 Avenue du Prof. Léon Bernard, CS 34317, CEDEX, 35043 Rennes, France

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Institut de Recherche en Santé, Environnement et Travail, IRSET Inserm U1085, Université de Rennes 1, 9 Avenue du Prof. Léon Bernard, 35000 Rennes, France

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Laboratoire de Synthèse et de Catalyse, Université Ibn Khaldoun, Tiaret 14000, Algeria

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Perha Pharmaceuticals & ManRos Therapeutics, “From Sea to Pharmacy”, Hôtel de Recherche, 29680 Roscoff, France

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Protein Phosphorylation & Human Disease Group, Station Biologique, 29680 Roscoff, France

Author to whom correspondence should be addressed.

Academic Editor: Daniela Catarzi

Pharmaceuticals 2021, 14(11), 1086; https://doi.org/10.3390/ph14111086

Received: 5 July 2021 / Revised: 21 October 2021 / Accepted: 22 October 2021 / Published: 27 October 2021

(This article belongs to the Special Issue Heterocyclic Compounds and Their Application in Therapy)

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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. View Full-Text

Keywords: microwave; Knoevenagel condensation; sulphur/nitrogen displacement; 1,3-thiazolidin-4-one; inhibition; protein kinase; DYRK1A; cell lines

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MDPI and ACS Style

Bourahla, K.; Guihéneuf, S.; Limanton, E.; Paquin, L.; Le Guével, R.; Charlier, T.; Rahmouni, M.; Durieu, E.; Lozach, O.; Carreaux, F.; Meijer, L.; Bazureau, J.-P. Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A. Pharmaceuticals 2021, 14, 1086. https://doi.org/10.3390/ph14111086

AMA Style

Bourahla K, Guihéneuf S, Limanton E, Paquin L, Le Guével R, Charlier T, Rahmouni M, Durieu E, Lozach O, Carreaux F, Meijer L, Bazureau J-P. Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A. Pharmaceuticals. 2021; 14(11):1086. https://doi.org/10.3390/ph14111086

Chicago/Turabian Style

Bourahla, Khadidja, Solène Guihéneuf, Emmanuelle Limanton, Ludovic Paquin, Rémy Le Guével, Thierry Charlier, Mustapha Rahmouni, Emilie Durieu, Olivier Lozach, François Carreaux, Laurent Meijer, and Jean-Pierre Bazureau. 2021. "Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A" Pharmaceuticals 14, no. 11: 1086. https://doi.org/10.3390/ph14111086

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Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A

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