Antimalarial Inhibitors Targeting Epigenetics or Mitochondria in Plasmodium falciparum: Recent Survey upon Synthesis and Biological Evaluation of Potential Drugs against Malaria

Molecules. 2021 Sep 21;26(18):5711. doi: 10.3390/molecules26185711.

Abstract

Despite many efforts, malaria remains among the most problematic infectious diseases worldwide, mainly due to the development of drug resistance by P. falciparum. Over the past decade, new essential pathways have been emerged to fight against malaria. Among them, epigenetic processes and mitochondrial metabolism appear to be important targets. This review will focus on recent evolutions concerning worldwide efforts to conceive, synthesize and evaluate new drug candidates interfering selectively and efficiently with these two targets and pathways. The focus will be on compounds/scaffolds that possess biological/pharmacophoric properties on DNA methyltransferases and HDAC's for epigenetics, and on cytochrome bc1 and dihydroorotate dehydrogenase for mitochondrion.

Keywords: activities; drug candidates; epigenetic; malaria; mitochondria; synthesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology
  • DNA / chemistry
  • Dihydroorotate Dehydrogenase
  • Drug Discovery
  • Drug Resistance
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Epigenesis, Genetic
  • Histone Deacetylases / metabolism
  • Humans
  • Malaria, Falciparum / drug therapy*
  • Methyltransferases / antagonists & inhibitors
  • Mitochondria / metabolism*
  • Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors
  • Plasmodium falciparum / drug effects*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Dihydroorotate Dehydrogenase
  • Enzyme Inhibitors
  • Quinazolines
  • DNA
  • Oxidoreductases Acting on CH-CH Group Donors
  • Methyltransferases
  • Histone Deacetylases