Zinc Dependent Histone Deacetylase Inhibitors in Cancer Therapeutics: Recent Update.

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.

journal_name

Curr Med Chem

authors

Sultana F,Manasa KL,Shaik SP,Bonam SR,Kamal A

doi

10.2174/0929867325666180530094120

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

7212-7280

issue

40

eissn

0929-8673

issn

1875-533X

pii

CMC-EPUB-90775

journal_volume

26

pub_type

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