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

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.

• Authors: Stephen Patterson, Alan H Fairlamb
• Journal: Current medicinal chemistry (Curr Med Chem) Vol. 26 Issue 23 Pg. 4454-4475 ( 2019) ISSN: 1875-533X [Electronic] United Arab Emirates
• PMID: 29701144 (Publication Type: Journal Article, Review)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Nitro Compounds
• Prodrugs
• Trypanocidal Agents

Topics

• Animals
• Humans
• Leishmaniasis (drug therapy)
• Molecular Structure
• Nitro Compounds (chemistry, pharmacology)
• Prodrugs (chemistry, pharmacology)
• Structure-Activity Relationship
• Trypanocidal Agents (chemistry, pharmacology)
• Trypanosomiasis (drug therapy)