Novel N-hydroxybenzamide-based HDAC inhibitors with branched CAP group.
Ongoing effort to gather further knowledge about the structural requirements on histone deacetylase inhibitors led to the synthesis of novel N-hydroxybenzamide-based HDAC inhibitors 1a-o, introducing branched hydrophobic groups at the capping group, and their inhibition activity against HDACs and anti-proliferation activity in four tumor cell lines were determined. Compounds 1j-o were further tested against recombinant human HDAC1 and HDAC4 to evaluate their selectivity profile. This work further suggests that the chemical nature of the capping group is critical for subtle discrimination between the class I and the class II HDAC isoforms.
Su
Hong
H
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Yu
Liqin
L
Nebbioso
Angela
A
Carafa
Vincenzo
V
Chen
Yadong
Y
Altucci
Lucia
L
You
Qidong
Q
D017209:Apoptosis; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D003001:Cloning, Molecular; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors*; D006655:Histone Deacetylases; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D020033:Protein Isoforms / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
D020033:Protein Isoforms; D012097:Repressor Proteins; C400300:HDAC4 protein, human; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases