Histone deacetylase inhibitors (HDACi) have been actively explored as anti-
cancer agents due to their ability to prevent deacetylation of
histones, resulting in uncoiling of
chromatin and stimulation of a range of genes associated in the regulation of cell survival, proliferation, differentiation and apoptosis. During the past several years, many HDACi have entered pre-clinical or clinical research as anti-
cancer agents with satisfying results. Out of these, more than 8 novel
hydroxamic acid based HDACi i.e.,
belinostat,
abexinostat, SB939,
resminostat,
givinostat,
quisinostat, pentobinostat,
CUDC-101 are in clinical trials and one of the
drug vorinostat (SAHA) has been approved by US FDA for
cutaneous T-cell lymphoma (CTCL). It is clear from the plethora of new molecules and the encouraging results from clinical trials that this class of
HDAC inhibitors hold a great deal of promise for the treatment of a variety of
cancers. In this review, we classified the
hydroxamic acid based HDACi on the basis of their structural features into saturated, unsaturated, branched, un-branched and 5, 6-membered cyclic ring linker present between
zinc binding group and connecting unit. The present article enlists reports on
hydroxamic acid based HDACi designed and developed using concepts of medicinal chemistry, demonstrating that hydroxamate derivatives represent a versatile class of compounds leading to novel imaging and therapeutic agents. This article will also provide a complete insight into various structural modifications required for optimum anticancer activity.