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Development of New 5-Arylidene-3-(arylmethyl)aminobutyl-2-thioxo-1,3-thiazolidine-4-one under Microwave Irradiation and Their Biological Effects on Protein Kinases and Tumoral Cell Lines
1  Université de Rennes 1, Institut des Sciences Chimiques de Rennes (ISCR), UMR CNRS 6226, Groupe ICMV, Bât. 10A, Campus de Beaulieu, 263 Av. du Général Leclerc, CS 74205, 35042 Rennes Cedex, France.
2  Laboratoire de Chimie Bio-Organique et de Substances Naturelles (LCBOSN), Université Nangui Abrogoua, Abidjan 02 BP 802, Côte d'Ivoire.

Published: 01 November 2016 by MDPI in 1st International Electronic Conference on Medicinal Chemistry session ECMC-1

Identification and development of new protein kinase inhibitors became these last two decades the key point for the search of new therapeutic agents because, the disorder of these enzymes in cellular environment is often the cause of pathologies as cancer and Alzheimer's disease (AD). In our laboratory, it was highlighted that N,N'-bis(5-arylidene-4-oxo-4,5-dihydrothiazolin-2-yl)aminopropylpiperazine (IC50 40 nM) presented selective inhibition towards the protein kinase DYRK1A [1,2] (dual specificity, tyrosine phosphorylation regulated kinases), enzyme suspected to have an impact on neurodegenerative diseases [3-5] and cancer [6]. To understand the mechanism of action towards DYRK1A and GSK3alpha/beta, we developed a route in 6 steps for a series of 5-arylidene-3-(arylmethyl)aminobutyl-2-thioxo-1,3-thiazolidine-4-ones. This methodology involved the construction of the 2-thioxo-1,3-thiazolidine-4-one platform under microwave irradiation from commercial bis(carboxymethyl)trithiocarbonate. The results of this multi-steps synthesis as well as the biological evaluations will be presented and discussed in this poster.

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