Biphenyl-4-yl-acrylohydroxamic acids: Identification of a novel indolyl-substituted HDAC inhibitor with antitumor activity

Cincinelli, Raffaella; Zwick, Vincent; Musso, Loana; Zuco, Valentina; De Cesare, Michelandrea; Zunino, Franco; Simoes Avello, Claudia; Nurisso, Alessandra; Giannini, Giuseppe; Cuendet, Muriel; Dallavalle, Sabrina

doi:10.1016/j.ejmech.2016.02.001

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Title		Biphenyl-4-yl-acrylohydroxamic acids: Identification of a novel indolyl-substituted HDAC inhibitor with antitumor activity
Authors		Cincinelli, Raffaella Zwick, Vincent Musso, Loana Zuco, Valentina De Cesare, Michelandrea Zunino, Franco Simoes Avello, Claudia Nurisso, Alessandra Giannini, Giuseppe Cuendet, Muriel Dallavalle, Sabrina show all authors [1 - 11]
Published in		European Journal of Medicinal Chemistry. 2016, vol. 112, p. 99-105
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.
Keywords		Antineoplastic Agents/chemistry/pharmacology — Apoptosis/drug effects — Biphenyl Compounds/chemistry/pharmacology — Colonic Neoplasms/drug therapy/metabolism — Drug Screening Assays — Antitumor — HCT116 Cells — Histone Deacetylase Inhibitors/chemistry/pharmacology — Histone Deacetylases/metabolism — Humans — Hydroxamic Acids/chemistry/pharmacology — Molecular Docking Simulation — Neoplasms/drug therapy/metabolism — Structure-Activity Relationship
Identifiers		DOI: 10.1016/j.ejmech.2016.02.001 PMID: 26890116
Full text		Article (Published version) (855 Kb) - Limited access to UNIGE
Structures		Faculté des sciences / Section des sciences pharmaceutiques
Citation (ISO format)		CINCINELLI, Raffaella et al. Biphenyl-4-yl-acrylohydroxamic acids: Identification of a novel indolyl-substituted HDAC inhibitor with antitumor activity. In: European Journal of Medicinal Chemistry, 2016, vol. 112, p. 99-105. doi: 10.1016/j.ejmech.2016.02.001 https://archive-ouverte.unige.ch/unige:94976