Targeting NAD-dependent dehydrogenases in drug discovery against infectious diseases and cancer

Biochem Soc Trans. 2020 Apr 29;48(2):693-707. doi: 10.1042/BST20191261.

Abstract

Dehydrogenases are oxidoreductase enzymes that play a variety of fundamental functions in the living organisms and have primary roles in pathogen survival and infection processes as well as in cancer development. We review here a sub-set of NAD-dependent dehydrogenases involved in human diseases and the recent advancements in drug development targeting pathogen-associated NAD-dependent dehydrogenases. We focus also on the molecular aspects of the inhibition process listing the structures of the most relevant molecules targeting this enzyme family. Our aim is to review the most impacting findings regarding the discovery of novel inhibitory compounds targeting the selected NAD-dependent dehydrogenases involved in cancer and infectious diseases.

Keywords: NAD biology; NAD dehydrogenases; cancer; drug discovery and design; malaria; tuberculosis.

Publication types

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

MeSH terms

  • Aldehyde Oxidoreductases / chemistry
  • Animals
  • Antimalarials / therapeutic use
  • Antitubercular Agents / therapeutic use
  • Communicable Diseases / drug therapy*
  • Drug Design
  • Drug Discovery*
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Humans
  • Inhibins / chemistry
  • Isoenzymes / chemistry
  • Malaria / drug therapy
  • NAD / chemistry*
  • Neoplasms / drug therapy*
  • Oxidoreductases / metabolism*
  • Tuberculosis / drug therapy

Substances

  • Antimalarials
  • Antitubercular Agents
  • Isoenzymes
  • inhibin-alpha subunit
  • NAD
  • Inhibins
  • Oxidoreductases
  • Aldehyde Oxidoreductases
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • aldehyde dehydrogenase (NAD(P)+)