Diverse classes of HDAC8 inhibitors: in search of molecular fingerprints that regulate activity.

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HDAC8 is one of the crucial enzymes involved in malignancy. Structural explorations of HDAC8 inhibitory activity and selectivity are required. A mathematical framework was constructed to explore important molecular fragments responsible for HDAC8 inhibition. Bayesian classification models were developed on a large set of structurally diverse HDAC8 inhibitors. This study helps to understand the structural importance of HDAC8 inhibitors. The hydrophobic aryl cap function is important for HDAC8 inhibition whereas benzamide moiety shows a negative impact on HDAC8 inhibition. This work validates our previously proposed structural features for better HDAC8 inhibition. The comparative learning between the statistical and intelligent methods will surely enrich future drug design aspects of HDAC8 inhibitors.