Title:The Redox Systems of Plasmodium falciparum and Plasmodium vivax: Comparison, In silico Analyses and Inhibitor Studies
Volume: 21
Issue: 15
Author(s): F. Mohring, J. Pretzel, E. Jortzik and K. Becker
Affiliation:
Keywords:
Antimalarials, disulfide reductase inhibitors, glutathione, malaria, oxidative stress, Plasmodium vivax, redox metabolism,
thioredoxin.
Abstract: Plasmodium falciparum is responsible for the most severe form of human malaria. P. vivax, in contrast, is the
most widespread malaria parasite with an enormous impact on health and economy, since the infection is characterized by
high rates of relapses. Due to the mild course of malaria tertiana and complicated in vitro culturing conditions of P. vivax,
most of the research on malaria parasites has focused on P. falciparum so far. The redox metabolism of P. falciparum is a
promising target for novel antimalarial drugs, since maintaining a redox equilibrium is of fundamental importance for the
parasite. P. falciparum contains a cytosolic glutathione and thioredoxin system, as well as redox systems in the apicoplast
and the mitochondrion. In contrast to P. falciparum, little is known about the redox processes in P. vivax so far. This review
summarizes the current knowledge of the redox metabolism in malaria parasites and provides a detailed in silico
comparison of the known and mostly well characterized redox enzymes from P. falciparum and the largely unknown redox
proteins from P. vivax. Known antimalarials at least partially mediating their antiparasitic activity by influencing the
redox balance of Plasmodium, including dehydroepiandrosterone, Mannich bases, methylene blue, and naphthoquinones,
are discussed. Furthermore, we present novel inhibitors identified via screening of a compound library from the Leibniz
Institute for Natural Product Research and Infection Biology, Jena that are active against the redox-related enzymes thioredoxin
reductase, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase 6-
phosphoglucono- lactonase from P. falciparum.
