Design, synthesis and biological evaluation of 1,4-benzodiazepine-2,5-dione-based HDAC inhibitors

Hydroxamic acids containing 1,4-benzodiazepine-2,5-dione cap structures have been synthesized and evaluated for their antiproliferative and HDAC-inhibitory activities against H661 cancer cells. New histone deacetylase inhibitors have been synthesized and evaluated for their activity against non-smal...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2007-09, Vol.17 (17), p.4819-4823
Main Authors: Loudni, Lynda, Roche, Joëlle, Potiron, Vincent, Clarhaut, Jonathan, Bachmann, Christian, Gesson, Jean-Pierre, Tranoy-Opalinski, Isabelle
Format: Article
Language:English
Subjects:
1,4-Benzodiazepine-2,5-dione
Antineoplastic agents
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Benzodiazepines - chemical synthesis
Benzodiazepines - chemistry
Benzodiazepines - pharmacology
Biological and medical sciences
Cell Line, Tumor
Chemistry, Pharmaceutical - methods
Cyclic peptide mimic
Cyclin-Dependent Kinase Inhibitor p21 - chemistry
Drug Design
Drug Screening Assays, Antitumor
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
General aspects
HDAC Inhibitors
Histone deacetylase
Histone Deacetylase Inhibitors
Histone Deacetylases - chemistry
Histones - chemistry
Humans
Medical sciences
Models, Chemical
Molecular Conformation
Pharmacology. Drug treatments
Protein Conformation
Tubulin - chemistry
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Summary:Hydroxamic acids containing 1,4-benzodiazepine-2,5-dione cap structures have been synthesized and evaluated for their antiproliferative and HDAC-inhibitory activities against H661 cancer cells. New histone deacetylase inhibitors have been synthesized and evaluated for their activity against non-small lung cancer cell line H661. These compounds have been designed with diversely substituted 1,4-benzodiazepine-2,5-dione moieties as cyclic peptide mimic cap structures, and a hydroxamate side chain. Biological evaluations demonstrated that benzodiazepine-based HDACi bearing an aromatic substituent at the N1 position exhibited promising antiproliferative and HDAC-inhibitory activities.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2007.06.067