Beilstein J. Org. Chem.2020,16, 628–637, doi:10.3762/bjoc.16.59
inhibitors (HDACis). The targets of interest (TOI) are analogues of panobinostat, one of the most potent and versatile HDACi reported. By simply replacing the phenyl core of panobinostat with that of a diazine derivative, docking studies against HDAC2 and HDAC8 revealed that the four analogues exhibit
inhibition activities comparable to that of panobinostat. Multistep syntheses afforded the visualized targets TOI1, TOI2, TOI3-rev and TOI4 whose biological evaluation confirmed the strength of HDAC8 inhibition with TOI4 displaying the greatest efficacy at varying concentrations. The results of this study
lay the foundation for future design strategies toward more potent HDACis for HDAC8 isozymes and further therapeutic applications for neuroblastoma.
Keywords: diazine; histone deacetylase; inhibitors; isozymes; panobinostat; Introduction
One of the most important posttranslational modifications
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Graphical Abstract
Figure 1:
Chemical structures of the target diazine-based surrogates for the central core of panobinostat.