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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