Synthesis, enzymatic inhibition, and cancer cell growth inhibition of novel delta-lactam-based histone deacetylase (HDAC) inhibitors.
delta-Lactam-based hydroxamic acids, inhibitors of histone deacetylase (HDAC), have been synthesized via ring closure metathesis of key diene intermediates followed by conversion to hydroxamic acid analogues. The hydroxamic acids 12a, 12b, and 17c showed potent inhibitory activity in HDAC enzyme assay. The hydroxamic acid 12b exhibited growth inhibitory activity on five human tumor cell lines, showing good sensitivity on the MDA-MB-231 breast tumor cell.
Kim
Hwan Mook
HM
Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-333, Republic of Korea.
Lee
Kiho
K
Park
Bum Woo
BW
Ryu
Dong Kyu
DK
Kim
Kangjeon
K
Lee
Chang Woo
CW
Park
Song-Kyu
SK
Han
Jung Whan
JW
Lee
Hee Yoon
HY
Lee
Hyun Yong
HY
Han
Gyoonhee
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors