Synthesis and modeling of new benzofuranone histone deacetylase inhibitors that stimulate tumor suppressor gene expression.
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.
Charrier
Cédric
C
Laboratoire Synthèse et Réactivité des Substances Naturelles, Université de Poitiers, CNRS-UMR 6514, 40 Avenue du Recteur Pineau, Poitiers F-86022, France.
Clarhaut
Jonathan
J
Gesson
Jean-Pierre
JP
Estiu
Guillermina
G
Wiest
Olaf
O
Roche
Joëlle
J
Bertrand
Philippe
P
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*
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