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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

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

Author(s): Stephen Patterson and Alan H. Fairlamb*

Volume 26, Issue 23, 2019

Page: [4454 - 4475] Pages: 22

DOI: 10.2174/0929867325666180426164352

Price: $65


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.

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

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