Design and synthesis of thiazole-5-hydroxamic acids as novel histone deacetylase inhibitors.
We have designed and synthesized a series of structurally novel hydroxamic acid-based histone deacetylase (HDAC) inhibitors characterized by a zinc chelating head group attached directly to a thiazole ring. The thiazole ring connects to a piperazine spacer, which is capped with a sulfonamide group. These novel molecules potently inhibit an HDAC enzyme mixture derived from HeLa cervical carcinoma cells and show potent antiproliferative activity against the breast cancer cell line MCF7.
Anandan
Sampath-Kumar
SK
EntreMed Inc., 101 College Street, Toronto Medical Discovery Tower, Toronto, Ontario, Canada M5G1L7. skumar@aretetherapeutics.com
Ward
John S
JS
Brokx
Richard D
RD
Denny
Trisha
T
Bray
Mark R
MR
Patel
Dinesh V
DV
Xiao
Xiao-Yi
XY
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship