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 language | English |
|---|---|
| Pages (from-to) | 4454-4475 |
| Number of pages | 22 |
| Journal | Current Medicinal Chemistry |
| Volume | 26 |
| Issue number | 23 |
| Early online date | 26 Apr 2018 |
| DOIs | |
| Publication status | Published - 2019 |
Keywords
- Chagas' disease
- Human African trypanosomiasis
- benznidazole
- delamanid
- fexinidazole
- nifurtimox
- nitro-drugs
- pretomanid
- visceral leishmaniasis.
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Pharmacology
- Drug Discovery
- Organic Chemistry
Access to Document
- Author Accepted Version
The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/openurl/content.php?genre=article&doi=10.2174/0929867325666180426164352.