In
this Perspective, we have brought together available biological
evidence on hydrazides as histone deacetylase inhibitors (HDACis)
and as a distinct type of Zn-binding group (ZBG) to be reviewed for
the first time in the literature. N-Alkyl hydrazides
have transformed the field, providing innovative and practical chemical
tools for selective and effective inhibition of specific histone deacetylase
(HDAC) enzymes, in addition to the usual hydroxamic acid and o-aminoanilide ZBG-bearing HDACis. This has enabled efficient
targeting of neurodegenerative diseases such as Alzheimer’s
disease, cancer, cardiovascular diseases, and protozoal pathologies.