Substituted N-(2-aminophenyl)-benzamides, (E)-N-(2-aminophenyl)-acrylamides and their analogues: novel classes of histone deacetylase inhibitors.
Inhibition of histone deacetylases (HDACs) is emerging as a new strategy in human cancer therapy. Novel 2-aminophenyl benzamides and acrylamides, that can inhibit human HDAC enzymes and induce hyperacetylation of histones in human cancer cells, have been designed and synthesized. These compounds selectively inhibit proliferation and cause cell cycle arrest in various human cancer cells but not in normal cells. The growth inhibition of 2-aminophenyl benzamides and acrylamides against human cancer cells in vitro is reversible and is dependent on the induction of histone acetylation. Compounds of this class can significantly reduce tumor growth in human tumor xenograft models.
Moradei
Oscar
O
MethylGene Inc., Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, QC, Canada H4S 2A1. moradeio@methylgene.com
Leit
Silvana
S
Zhou
Nancy
N
Fréchette
Sylvie
S
Paquin
Isabelle
I
Raeppel
Stéphane
S
Gaudette
Frédéric
F
Bouchain
Giliane
G
Woo
Soon H
SH
Vaisburg
Arkadii
A
Fournel
Marielle
M
Kalita
Ann
A
Lu
Aihua
A
Trachy-Bourget
Marie-Claude
MC
Yan
Pu T
PT
Liu
Jianhong
J
Li
Zuomei
Z
Rahil
Jubrail
J
MacLeod
A Robert
AR
Besterman
Jeffrey M
JM
Delorme
Daniel
D
D000178:Acrylamides / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D013329:Structure-Activity Relationship
D000178:Acrylamides; D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors