Background: Histone deacetylases (HDAC) are an important class of enzymes that
play a pivotal role in epigenetic regulation of gene expression that modifies the terminal of
core histones leading to remodelling of chromatin topology and thereby controlling gene expression.
HDAC inhibitors (HDACi) counter this action and can result in hyperacetylation of
histones, thereby inducing an array of cellular consequences such as activation of apoptotic
pathways, generation of reactive oxygen species, cell cycle arrest and autophagy. Hence, there
is a growing interest in the potential clinical use of HDAC inhibitors as a new class of targeted
Methodology and Result: Several research articles spanning between 2016 and 2017 were
reviewed in this article and presently offer critical insights into the important strategies such
as structure-based rational drug design, multi-parameter lead optimization methodologies,
relevant SAR studies and biology of various class of HDAC inhibitors, such as hydroxamic
acids, benzamides, cyclic peptides, aliphatic acids, summarising the clinical trials and results
of various combination drug therapy till date.
Conclusion: This review will provide a platform to the synthetic chemists and biologists to
cater the needs of both molecular targeted therapy and combination drug therapy to design
and synthesize safe and selective HDAC inhibitors in cancer therapeutics.
Keywords: Aliphatic acids, benzanilides, cancer therapeutics, cyclic peptides, histone deacetylases, histone deacetylase inhibitors, hydroxamic acids.
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