Structure-activity relationship studies of a series of novel delta-lactam-based histone deacetylase inhibitors.
We synthesized a series of delta-lactam-based HDAC inhibitors that were identified with various degrees of anti-inflammatory and cell growth inhibitory activities. Compounds possessing significant HDAC inhibitory activity exhibited both anti-inflammatory and cell growth inhibitory activities as well as significant tumor growth inhibition in the in vivo tumor xenograft experiments. Besides, these compounds demonstrated anti-inflammatory properties in vitro via suppression of the production of the proinflammatory cytokine TNF-alpha and nitric oxide by LPS-stimulated RAW264.7 cells.
Kim
Hwan Mook
HM
Bioevaluation Center, KRIBB, Daejeon 305-806, Korea.
Ryu
Dong-Kyu
DK
Choi
Yongseok
Y
Park
Bum Woo
BW
Lee
Kiho
K
Han
Sang Bae
SB
Lee
Chang-Woo
CW
Kang
Moo-Rim
MR
Kang
Jong Soon
JS
Boovanahalli
Shanthaveerappa K
SK
Park
Song-Kyu
SK
Han
Jung Whan
JW
Chun
Tae-Gyu
TG
Lee
Hee-Yoon
HY
Nam
Ky-Youb
KY
Choi
Eun Hyun
EH
Han
Gyoonhee
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D007769:Lactams; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide