Journal Image
Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
Epub Full Text Article
DOI: 10.2174/09298673113209990191      Price:  $95

A Structural Insight into Hydroxamic Acid Based Histone Deacetylase Inhibitors for the Presence of Anticancer Activity

Author(s): H. Rajak, A. Singh, K. Raghuwanshi, R. Kumar, P.K. Dewangan, R. Veerasamy, P.C. Sharma, A. Dixit and P. Mishra
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 HDACi 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, unbranched 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.
Anticancer agents, belinostat, givinostat, histone, histone deacetylase inhibitors, hydroxamic acid, panobinostat, vorinostat
SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur-495 009 (CG) India.