title: Synthetic Development of New 3-(4-Arylmethylamino)butyl-5-arylidene-rhodanines under Microwave Irradiation and Their Effects on Tumor Cell Lines and against Protein Kinases.
abstract: A new route to 3-(4-arylmethylamino)butyl-5-arylidene-2-thioxo-1,3-thiazolidine-4-one 9 was developed in six steps from commercial 1,4-diaminobutane 1 as starting material. The key step of this multi-step synthesis involved a solution phase "one-pot two-steps" approach assisted by microwave dielectric from N-(arylmethyl)butane-1,4-diamine hydrochloride 6a-f (as source of the first point diversity) and commercial bis-(carboxymethyl)-trithiocarbonate reagent 7 for construction of the rhodanine platform. This platform was immediately functionalized by Knoevenagel condensation under microwave irradiation with a series of aromatic aldehydes 3 as second point of diversity. These new compounds were prepared in moderate to good yields and the fourteen synthetic products 9a-n have been obtained with a Z-geometry about their exocyclic double bond. These new 5-arylidene rhodanines derivatives 9a-n were tested for their kinase inhibitory potencies against four protein kinases: Human cyclin-dependent kinase 5-p25, HsCDK5-p25; porcine Glycogen Synthase Kinase-3, GSK-3α/β; porcine Casein Kinase 1, SsCK1 and human HsHaspin. They have also been evaluated for their in vitro inhibition of cell proliferation (HuH7 D12, Caco 2, MDA-MB 231, HCT 116, PC3, NCI-H727, HaCat and fibroblasts). Among of all these compounds, 9j presented selective micromolar inhibition activity on SsCK1 and 9i exhibited antitumor activities in the HuH7 D12, MDA-MBD231 cell lines.
authors.affiliation: Université de Rennes 1, Institut des Sciences Chimiques de Rennes (ISCR), UMR CNRS 6226, Groupe ICMV, Bât. 10A, Campus de Beaulieu, 263 Avenue du Général Leclerc, CS 74205, 35042 Rennes Cedex, France. deliko.dago@univ-rennes1.fr.|Laboratoire de Chimie Bio-Organique et de Substances Naturelles (LCBOSN), Université Nangui Abrogoua, Abidjan 02, BP 802, Cote d'Ivoire. deliko.dago@univ-rennes1.fr.
authors.forename: Camille Déliko
authors.initials: CD
authors.lastname: Dago
authors.affiliation: Université de Rennes 1, Institut des Sciences Chimiques de Rennes (ISCR), UMR CNRS 6226, Groupe ICMV, Bât. 10A, Campus de Beaulieu, 263 Avenue du Général Leclerc, CS 74205, 35042 Rennes Cedex, France. christelle.ambeu@univ-rennes1.fr.|Laboratoire de Chimie Bio-Organique et de Substances Naturelles (LCBOSN), Université Nangui Abrogoua, Abidjan 02, BP 802, Cote d'Ivoire. christelle.ambeu@univ-rennes1.fr.
authors.forename: Christelle N'ta
authors.initials: CN
authors.lastname: Ambeu
authors.affiliation: UFR des Sciences Biologiques, Université de Péléforo Gon Coulibaly, Korhogo, BP 1328, Cote d'Ivoire. wacothon@yahoo.fr.
authors.forename: Wacothon-Karime
authors.initials: WK
authors.lastname: Coulibaly
authors.affiliation: Laboratoire de Chimie Bio-Organique et de Substances Naturelles (LCBOSN), Université Nangui Abrogoua, Abidjan 02, BP 802, Cote d'Ivoire. bekro2001@yahoo.fr.
authors.forename: Yves-Alain
authors.initials: YA
authors.lastname: Békro
authors.affiliation: Laboratoire de Chimie Bio-Organique et de Substances Naturelles (LCBOSN), Université Nangui Abrogoua, Abidjan 02, BP 802, Cote d'Ivoire. kojanova1926@hotmail.fr.
authors.forename: Janat
authors.initials: J
authors.lastname: Mamyrbékova
authors.affiliation: Station Biologique de Roscoff, USR 3151, CNRS-UPMC, Kinase Inhibitory Specialized Screening facility, KISSf, Place George Teissier, BP 74, 29682 Roscoff, France. audrey.defontaine@sb-roscoff.fr.
authors.forename: Audrey
authors.initials: A
authors.lastname: Defontaine
authors.affiliation: Station Biologique de Roscoff, USR 3151, CNRS-UPMC, Kinase Inhibitory Specialized Screening facility, KISSf, Place George Teissier, BP 74, 29682 Roscoff, France. blandine.baratte@sb-roscoff.fr.
authors.forename: Blandine
authors.initials: B
authors.lastname: Baratte
authors.affiliation: Station Biologique de Roscoff, USR 3151, CNRS-UPMC, Kinase Inhibitory Specialized Screening facility, KISSf, Place George Teissier, BP 74, 29682 Roscoff, France. stephane.bach@sb-roscoff.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bach
authors.affiliation: Station Biologique de Roscoff, USR 3151, CNRS-UPMC, Kinase Inhibitory Specialized Screening facility, KISSf, Place George Teissier, BP 74, 29682 Roscoff, France. sandrine.ruchaud@sb-roscoff.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ruchaud
authors.affiliation: Université de Rennes 1, ImPACcell, SFR Biosit, Bât. 8, 2 Avenue du Professeur Léon Bernard, CS 34317, 35043 Rennes Cedex, France. remy.leguevel@univ-rennes1.fr.
authors.forename: Rémy Le
authors.initials: RL
authors.lastname: Guével
authors.affiliation: Université de Rennes 1, ImPACcell, SFR Biosit, Bât. 8, 2 Avenue du Professeur Léon Bernard, CS 34317, 35043 Rennes Cedex, France. myriam.ravache@gmail.com.
authors.forename: Myriam
authors.initials: M
authors.lastname: Ravache
authors.affiliation: Université de Rennes 1, ImPACcell, SFR Biosit, Bât. 8, 2 Avenue du Professeur Léon Bernard, CS 34317, 35043 Rennes Cedex, France. anne.corlu@univ-rennes1.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Corlu
authors.affiliation: Université de Rennes 1, Institut des Sciences Chimiques de Rennes (ISCR), UMR CNRS 6226, Groupe ICMV, Bât. 10A, Campus de Beaulieu, 263 Avenue du Général Leclerc, CS 74205, 35042 Rennes Cedex, France. jean-pierre.bazureau@univ-rennes1.fr.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bazureau
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology; D018938:Caco-2 Cells; D047389:Casein Kinase I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D045325:HCT116 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008872:Microwaves; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011700:Putrescine / Q000737:chemistry; D013329:Structure-Activity Relationship; D013552:Swine; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013871:Thiones / Q000737:chemistry
chemical_list: D000447:Aldehydes; D018906:Antineoplastic Agents, Alkylating; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D053778:Thiazolidines; D013871:Thiones; D047389:Casein Kinase I; D051360:Cyclin-Dependent Kinase 5; D000071679:Glycogen Synthase Kinase 3 beta; C530656:HASPIN protein, human; D017346:Protein Serine-Threonine Kinases; C495905:CDK5 protein, human; D038362:Glycogen Synthase Kinase 3; D011700:Putrescine
keywords: 5-arylidene rhodanine; Alzheimer’s disease; HsCDK5-p25; Knoevenagel condensation; SsCK1; cancer; cell lines; inhibitor; one-pot two-steps; protein kinase