Stephen Patterson and Alan H. Fairlamb* Pages 4454 - 4475 ( 22 )
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.
Human African trypanosomiasis, Chagas' disease, visceral leishmaniasis, nifurtimox, benznidazole, fexinidazole, pretomanid, delamanid, nitro-drugs.
Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee