title: Novel inhibitors of human histone deacetylases: design, synthesis and bioactivity of 3-alkenoylcoumarines.
abstract: Histone deacetylases (HDACs) are well-established, promising targets for anticancer therapy due to their critical role in cancer development. Accordingly, an increasing number of HDAC inhibitors displaying cytotoxic effects against cancer cells have been reported. Among them, a large panel of chemical structures was described including coumarin-containing molecules. In this study, we described synthesis and biological activity of new coumarin-based derivatives as HDAC inhibitors. Among eight derivatives, three compounds showed HDAC inhibitory activities and antitumor activities against leukemia cell lines without affecting the viability of peripheral blood mononuclear cells from healthy donors.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, L-2540 Luxembourg, Luxembourg.
authors.forename: Carole
authors.initials: C
authors.lastname: Seidel
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, L-2540 Luxembourg, Luxembourg.
authors.forename: Michael
authors.initials: M
authors.lastname: Schnekenburger
authors.affiliation: UMR CNRS 7565 SRSMC, Université de Lorraine, 57070 Metz, France.
authors.forename: Clemens
authors.initials: C
authors.lastname: Zwergel
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, L-2540 Luxembourg, Luxembourg.
authors.forename: François
authors.initials: F
authors.lastname: Gaascht
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, L-2540 Luxembourg, Luxembourg.
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.affiliation: UMR CNRS 7565 SRSMC, Université de Lorraine, 57070 Metz, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Kirsch
authors.affiliation: UMR CNRS 7565 SRSMC, Université de Lorraine, 57070 Metz, France; Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Roma, Italy. Electronic address: sergio.valente@uniroma1.it.
authors.forename: Sergio
authors.initials: S
authors.lastname: Valente
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Building 20 Room 303, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea. Electronic address: marcdiederich@snu.ac.kr.
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases
keywords: Anti-proliferative activity; Cancer; Chalcone; Coumarin; Histone deacetylase inhibitors