Structural features for HDAC6 inhibitory specificity of Salvia corrugata Vahl. diterpene α-hydroxyquinones

Histone deacetylases (HDACs) are enzymes that deacetylate lysine residues from histones as well as from several other nuclear, cytoplasmic and mitochondrial non-histone proteins. In mammals, 11 zinc-dependent HDACs have been classified into three classes: Class I (HDACs 1 to 3 and HDAC8), class II which is subdivided into classes IIa (HDAC4, 5, 7, and 9) and IIb (HDAC6and 10), and class IV (HDAC11) [1]. Because of its central role in memory, protein aggregate elimination, neuronal oxidative stress and mitochondrial functions, HDAC6 appears as a promising target for Alzheimer's disease [1, 2]. However, developing new selective HDAC6 inhibitors is a challenge and their design is usually based on structural modifications on the cap portion, which is separated from a zinc-binding group by a linker portion [2]. Aims: To search for potential structural features within natural scaffolds which are able to provide isoform inhibitory specificity for HDAC6 compared to class I HDACs.