title: Biphenyl-4-yl-acrylohydroxamic acids: Identification of a novel indolyl-substituted HDAC inhibitor with antitumor activity.
abstract: Modification of the cap group of biphenylacrylohydroxamic acid-based HDAC inhibitors led to the identification of a new derivative (3) characterized by an indolyl-substituted 4-phenylcinnamic skeleton. Molecular docking was used to predict the optimal conformation in the class I HDACs active site. Compound 3 showed HDAC inhibitory activity and antiproliferative activity against a panel of tumor cell lines, in the low μM range. The compound was further tested in vitro for acetylation of histone H4 and other non-histone proteins, and in vivo in a colon carcinoma model, showing significant proapoptotic and antitumor activities.
authors.affiliation: Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, University of Milan, via Celoria 2, 20133 Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cincinelli
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva 11, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Zwick
authors.affiliation: Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, University of Milan, via Celoria 2, 20133 Milan, Italy.
authors.forename: Loana
authors.initials: L
authors.lastname: Musso
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Zuco
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milano, Italy.
authors.forename: Michelandrea
authors.initials: M
authors.lastname: De Cesare
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133 Milano, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva 11, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Simoes-Pires
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva 11, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nurisso
authors.affiliation: R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Via Pontina Km 30,400, I-00071 Pomezia, Roma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva 11, Switzerland.
authors.forename: Muriel
authors.initials: M
authors.lastname: Cuendet
authors.affiliation: Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, University of Milan, via Celoria 2, 20133 Milan, Italy. Electronic address: sabrina.dallavalle@unimi.it.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dallavalle
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D006655:Histone Deacetylases
keywords: Antiproliferative activity; Antitumor activity; HDAC inhibitors; Hydroxamic acids; Synthesis