Novel inhibitors of the Plasmodium falciparum electron transport chain

Parasitology. 2014 Jan;141(1):50-65. doi: 10.1017/S0031182013001571.

Abstract

Due to an increased need for new antimalarial chemotherapies that show potency against Plasmodium falciparum, researchers are targeting new processes within the parasite in an effort to circumvent or delay the onset of drug resistance. One such promising area for antimalarial drug development has been the parasite mitochondrial electron transport chain (ETC). Efforts have been focused on targeting key processes along the parasite ETC specifically the dihydroorotate dehydrogenase (DHOD) enzyme, the cytochrome bc 1 enzyme and the NADH type II oxidoreductase (PfNDH2) pathway. This review summarizes the most recent efforts in antimalarial drug development reported in the literature and describes the evolution of these compounds.

Publication types

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

MeSH terms

  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Electron Transport / drug effects*
  • Electron Transport Complex III / antagonists & inhibitors
  • Electron Transport Complex III / chemistry
  • Electron Transport Complex III / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / parasitology
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Molecular Docking Simulation
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors
  • NADH, NADPH Oxidoreductases / chemistry
  • NADH, NADPH Oxidoreductases / metabolism
  • Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors
  • Oxidoreductases Acting on CH-CH Group Donors / chemistry
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / enzymology
  • Protozoan Proteins / antagonists & inhibitors*
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Enzyme Inhibitors
  • Protozoan Proteins
  • Oxidoreductases Acting on CH-CH Group Donors
  • dihydroorotate dehydrogenase
  • NADH, NADPH Oxidoreductases
  • Electron Transport Complex III