Parasitic sirtuin 2 as an opportunity in drug discovery

Future Med Chem. 2021 Aug;13(16):1397-1409. doi: 10.4155/fmc-2021-0091. Epub 2021 Jun 30.

Abstract

Infections caused by protozoans remain a public health issue, especially in tropical countries. Serious adverse events, lack of efficacy at the different stages of the infection and routes of administration that have a negative impact on treatment adherence are some of the problems with currently available therapy against these diseases. Here we describe an epigenetic target, sirtuin 2 and its related proteins, that is promising given the results in phenotypic assays and in vivo models against Sir2 of Plasmodium falciparum, Leishmania donovani, Leishmania infantum, Schistosoma mansoni, Trypanosoma brucei and Trypanosoma cruzi parasites. The results we present highlight how this target can be extensively explored and how its inhibitors might be employed in the clinic.

Keywords: HDAC; drug design; epigenetics; sirtuin 2; tropical diseases.

Publication types

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

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Drug Discovery*
  • Humans
  • Leishmania / drug effects
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects
  • Schistosoma mansoni / drug effects
  • Sirtuin 2 / antagonists & inhibitors*
  • Sirtuin 2 / metabolism
  • Trypanosoma / drug effects

Substances

  • Antiprotozoal Agents
  • Sirtuin 2