Current and Future Prospects of Nitro-compounds as Drugs for Trypanosomiasis and Leishmaniasis

Alan H. Fairlamb (Lead / Corresponding author), Stephen Patterson

Research output: Contribution to journalReview article

10 Citations (Scopus)
257 Downloads (Pure)

Abstract

Interest in nitroheterocyclic drugs for the treatment of infectious diseases has undergone a resurgence in recent years. Here we review the current status of monocyclic and bicyclic nitroheterocyclic compounds as existing or potential new treatments for visceral leishmaniasis, Chagas' disease and human African trypanosomiasis. Both monocyclic (nifurtimox, benznidazole and fexinidazole) and bicyclic (pretomanid (PA-824) and delamanid (OPC-67683)) nitro-compounds are prodrugs, requiring enzymatic activation to exert their parasite toxicity. Current understanding of the nitroreductases involved in activation and possible mechanisms by which parasites develop resistance is discussed along with a description of the pharmacokinetic / pharmacodynamic behaviour and chemical structure-activity relationships of drugs and experimental compounds.

Original languageEnglish
Pages (from-to)4454-4475
Number of pages22
JournalCurrent Medicinal Chemistry
Volume26
Issue number23
Early online date26 Apr 2018
DOIs
Publication statusPublished - 2019

Keywords

  • Chagas' disease
  • Human African trypanosomiasis
  • benznidazole
  • delamanid
  • fexinidazole
  • nifurtimox
  • nitro-drugs
  • pretomanid
  • visceral leishmaniasis.

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