Development of potential antitumor agents. Synthesis and biological evaluation of a new set of sulfonamide derivatives as histone deacetylase inhibitors.
A series of sulfonamide hydroxamic acids and anilides have been synthesized and studied as histone deacetylase (HDAC) inhibitors that can induce hyperacetylation of histones in human cancer cells. The inhibition of HDAC activity represents a novel approach for intervening in cell cycle regulation. The lead candidates were screened in a panel of human tumor and normal cell lines. They selectively inhibit proliferation, cause cell cycle blocks, and induce apoptosis in human cancer cells but not in normal cells. The structure-activity relationships, the antiproliferative activity, and the in vivo efficacy are described.
Bouchain
Giliane
G
Department of Medicinal Chemistry, MethylGene Inc., 7220 Frederick-Banting, Montréal, Québec H4S 2A1, Canada.
Leit
Silvana
S
Frechette
Sylvie
S
Khalil
Elie Abou
EA
Lavoie
Rico
R
Moradei
Oscar
O
Woo
Soon Hyung
SH
Fournel
Marielle
M
Yan
Pu T
PT
Kalita
Ann
A
Trachy-Bourget
Marie-Claude
MC
Beaulieu
Carole
C
Li
Zuomei
Z
Robert
Marie-France
MF
MacLeod
A Robert
AR
Besterman
Jeffrey M
JM
Delorme
Daniel
D
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013449:Sulfonamides