title: Modification of cap group in delta-lactam-based histone deacetylase (HDAC) inhibitors.
abstract: Novel delta-lactam-based HDAC inhibitors which have various substituted benzyl, bi-aromatic cap groups were prepared using ring closure metathesis reaction, and evaluated their HDAC inhibitory activities and anti-proliferative effects. Among prepared analogues, 11m and 11o have very strong HDAC enzymatic inhibition and showed the most potent growth inhibitory activity to five human tumor cell lines including PC-3, ACHN, NUGC-3, HCT-15, and MBA-MB-231 tumor cell lines. Compounds 11m and 11o also showed good tumor growth inhibition of MDA-MB-231 cells in in vivo xenograft model. Structure-activity relationship study using docking model explained the significance of hydrophobic aromatic cap groups for their in vitro activities.
authors: Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-333, Republic of Korea.
authors: Hwan Mook
authors: HM
authors: Kim
authors: Sung Hee
authors: SH
authors: Hong
authors: Myung Sook
authors: MS
authors: Kim
authors: Chang Woo
authors: CW
authors: Lee
authors: Jong Soon
authors: JS
authors: Kang
authors: Kiho
authors: K
authors: Lee
authors: Song-Kyu
authors: SK
authors: Park
authors: Jeung Whan
authors: JW
authors: Han
authors: Hee Yoon
authors: HY
authors: Lee
authors: Yongseok
authors: Y
authors: Choi
authors: Ho Jeung
authors: HJ
authors: Kwon
authors: Gyoonhee
authors: G
authors: Han
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D056572:Histone Deacetylase Inhibitors; D007769:Lactams; D006655:Histone Deacetylases