Lactate dehydrogenase and malate dehydrogenase: Potential antiparasitic targets for drug development studies

Bioorg Med Chem. 2021 Nov 15:50:116458. doi: 10.1016/j.bmc.2021.116458. Epub 2021 Oct 9.

Abstract

Parasitic diseases remain a major public health concern for humans, claiming millions of lives annually. Although different treatments are required for these diseases, drug usage is limited due to the development of resistance and toxicity, which necessitate alternative therapies. It has been shown in the literature that parasitic lactate dehydrogenases (LDH) and malate dehydrogenases (MDH) have unique pharmacological selective and specificity properties compared to other isoforms, thus highlighting them as viable therapeutic targets involved in aerobic and anaerobic glycolytic pathways. LDH and MDH are important therapeutic targets for invasive parasites because they play a critical role in the progression and development of parasitic diseases. Any strategy to impede these enzymes would be fatal to the parasites, paving the way to develop and discover novel antiparasitic agents. This review aims to highlight the importance of parasitic LDH and MDH as therapeutic drug targets in selected obligate apicoplast parasites. To the best of our knowledge, this review presents the first comprehensive review of LDH and MDH as potential antiparasitic targets for drug development studies.

Keywords: Cryptosporidium parvum; Lactate dehydrogenase; Malate dehydrogenase; Plasmodium falciparum; Schistosoma haematobium.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiparasitic Agents / chemical synthesis
  • Antiparasitic Agents / chemistry
  • Antiparasitic Agents / pharmacology*
  • Cryptosporidium parvum / drug effects
  • Cryptosporidium parvum / enzymology
  • Drug Development*
  • Humans
  • L-Lactate Dehydrogenase / antagonists & inhibitors*
  • L-Lactate Dehydrogenase / metabolism
  • Malate Dehydrogenase / antagonists & inhibitors*
  • Malate Dehydrogenase / metabolism
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium / drug effects
  • Plasmodium / enzymology
  • Schistosoma / drug effects
  • Schistosoma / enzymology
  • Toxoplasma / drug effects
  • Toxoplasma / enzymology
  • Trichomonas vaginalis / drug effects
  • Trichomonas vaginalis / enzymology

Substances

  • Antiparasitic Agents
  • L-Lactate Dehydrogenase
  • Malate Dehydrogenase