title: Synthesis and modeling of new benzofuranone histone deacetylase inhibitors that stimulate tumor suppressor gene expression.
abstract: New benzofuranones were synthesized and evaluated toward NCI-H661 non-small cell lung cancer cells. Benzamide derivatives possessed micromolar antiproliferative and histone deacetylase inhibitory activities and modulate histone H4 acetylation. Hydroxamic acids were found to be potent nanomolar antiproliferative agents and HDAC inhibitors. Computational analysis presented a rationale for the activities of the hydroxamate derivatives. Impact of the HDAC inhibition on the expression of E-cadherin and the SEMA3F tumor suppressor genes revealed new promising compounds for lung cancer treatments.
authors.affiliation: Laboratoire Synthèse et Réactivité des Substances Naturelles, Université de Poitiers, CNRS-UMR 6514, 40 Avenue du Recteur Pineau, Poitiers F-86022, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Charrier
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clarhaut
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gesson
authors.forename: Guillermina
authors.initials: G
authors.lastname: Estiu
authors.forename: Olaf
authors.initials: O
authors.lastname: Wiest
authors.forename: Joëlle
authors.initials: J
authors.lastname: Roche
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D001572:Benzofurans; D015820:Cadherins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C491230:SEMA3F protein, human; D014404:Tubulin; D025521:Tumor Suppressor Proteins; D006655:Histone Deacetylases