From natural products to HDAC inhibitors: An overview of drug discovery and design strategy

Bioorg Med Chem. 2021 Dec 15:52:116510. doi: 10.1016/j.bmc.2021.116510. Epub 2021 Nov 10.

Abstract

Histone deacetylases (HDACs) play a key role in the homeostasis of protein acetylation in histones and have recently emerged as a therapeutic target for numerous diseases. The inhibition of HDACs may block angiogenesis, arrest cell growth, and lead to differentiation and apoptosis in tumour cells. Thus, HDAC inhibitors (HDACi) have received increasing attention and many of which are developed from natural sources. In the past few decades, naturally occurring HDACi have been identified to have potent anticancer activities, some of which have demonstrated promising therapeutic effects on haematological malignancies. In this review, we summarized the discovery and modification of HDAC inhibitors from natural sources, novel drug design that uses natural products as parent nuclei, and dual target design strategies that combine HDAC with non-HDAC targets.

Keywords: Drug design; Histone deacetylase inhibitor; Natural products; Structural modification.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biological Products / chemical synthesis
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Drug Design*
  • Drug Discovery*
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism*
  • Humans
  • Molecular Structure

Substances

  • Biological Products
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases