title: Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance.
abstract: Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drug-resistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes.
authors.affiliation: UCIBIO/REQUIMTE, Chemistry and Biochemistry Department, Faculty of Sciences, University of Porto, Porto, Portugal nuno.vale@fc.up.pt.
authors.forename: Nuno
authors.initials: N
authors.lastname: Vale
authors.affiliation: UCIBIO/REQUIMTE, Chemistry and Biochemistry Department, Faculty of Sciences, University of Porto, Porto, Portugal.|Center for the Study of Animal Science, ICETA, Porto, University of Porto, Portugal.|ICBAS-University of Porto, Porto, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Gouveia
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rinaldi
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
authors.affiliation: ICBAS-University of Porto, Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.|Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Gärtner
authors.affiliation: Center for the Study of Animal Science, ICETA, Porto, University of Porto, Portugal.|INSA-National Health Institute Dr. Ricardo Jorge, Porto, Portugal.
authors.forename: José M
authors.initials: JM
authors.lastname: Correia da Costa
mesh_terms: D017954:Africa South of the Sahara; D000818:Animals; D004351:Drug Resistance; D006801:Humans; D011223:Praziquantel / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D012547:Schistosoma / Q000187:drug effects* / Q000378:metabolism; D012552:Schistosomiasis / Q000188:drug therapy*; D012556:Schistosomicides / Q000378:metabolism* / Q000627:therapeutic use*
chemical_list: D012556:Schistosomicides; D011223:Praziquantel
keywords: cytochromes P450; enantiomers; metabolism; praziquantel; schistosomiasis