Design, synthesis and biological evaluation of 1,4-benzodiazepine-2,5-dione-based HDAC inhibitors.
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.
Loudni
Lynda
L
Université de Poitiers, CNRS UMR 6514, SRSN, 40 Avenue du Recteur Pineau, 86022, Poitiers, France.
Roche
Joëlle
J
Potiron
Vincent
V
Clarhaut
Jonathan
J
Bachmann
Christian
C
Gesson
Jean-Pierre
JP
Tranoy-Opalinski
Isabelle
I
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000737:chemistry; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry; D006657:Histones / Q000737:chemistry; D006801:Humans; D008956:Models, Chemical; D008968:Molecular Conformation; D011487:Protein Conformation; D014404:Tubulin / Q000737:chemistry
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D014404:Tubulin; D001569:Benzodiazepines; D006655:Histone Deacetylases; C468549:Bz-423