Zinc dependent histone deacetylase inhibitors in cancer therapeutics: Recent update

Faria Sultana, Kesari Lakshmi Manasa, Siddiq Pasha Shaik, Srinivasa Reddy Bonam, Ahmed Kamal

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)7212-7280
Number of pages69
JournalCurrent Medicinal Chemistry
Volume26
Issue number40
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

  • Aliphatic acids
  • Benzanilides
  • Cancer therapeutics
  • Cyclic peptides
  • Histone deacetylase inhibitors and hydroxamic acids
  • Histone deacetylases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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