Affiliation:
1. Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500007, India
2. Vaccine Immunology Laboratory, Natural Product Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India
Abstract
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 (ROS), 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 cancer therapeutics.
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.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
Cited by
15 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献