Background: Dysregulation of HDACs has been associated with tumour development
and therefore inhibiting HDAC’s have surfaced as promising therapeutic strategy
Methods: Vorinostat analogues with different biological activities were investigated for
underlying structure-activity relationship.
Results: Out of six activities and their multiple QSAR models, HDAC1 and HDAC8 produced
statistically fit, stable and predictive linear (MLR) and non-linear (SVM) QSAR
models. In case of HDAC1 activity as end point, linear (R2=0.8089, R2
non-linear (R2=0.9801, R2
CV=0.8952) QSAR models turned reliable to investigate SAR.
Similarly, HDAC8 activity based linear (R2=0.9454, R2
CV=0.9049) and non-linear
CV=0.9232) QSAR models produced statistically improved and stable models.
Conclusion: Molecular descriptors derived from 3-D Morse and Radial Distribution Function indices were
found to be selective in all the models. These molecular descriptors which encode common SAR among Vorinostat
derivatives were evaluated for their potent HDAC inhibition activity.