Table 1.

The hydroxamic acid moiety is important for the effects of droxinostat on HDAC activity and FAS sensitization

CompoundStructureHDAC IC50 (μmol/L)LD50 −FAS (μmol/L)LD50 +FAS (μmol/L)
Droxinostat (1)10 ± 1>8020 ± 2
2>80>80>80
3>80>80>80

NOTE: Extracts from HeLa cells were treated with increasing concentrations of droxinostat and analogues 2 and 3 with substituted hydroxamic acid moieties, and deacetylase activity was measured as described in Materials and Methods. The IC50 represents the concentration of the compound to inhibit 50% of the deacetylase activity compared with control-treated extracts. PPC-1 cells were treated with increasing concentrations of droxinostat and analogues 2 and 3 with substituted hydroxamic acid moieties with and without FAS (100 ng/mL). Sixteen hours after incubation, cell growth and viability were determined by the MTS assay. Data represent the mean ± SD of independent experiments done in triplicate.