Primaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms

dc.creatorAguiar, Anna Caroline Campos
dc.creatorFigueiredo, Flávio Júnior Barbosa
dc.creatorNeuenfeldt, Patrícia Devantier
dc.creatorKatsuragawa, Tony Hiroshi
dc.creatorDrawanz, Bruna Bento
dc.creatorCunico, Wilson
dc.creatorSinnis, Photini
dc.creatorZavala, Fidel
dc.creatorKrettli, Antoniana Ursine
dc.date2018-05-22T18:58:32Z
dc.date2018-05-22T18:58:32Z
dc.date2017
dc.date.accessioned2023-09-26T20:08:42Z
dc.date.available2023-09-26T20:08:42Z
dc.identifierAGUIAR, Anna Caroline Campos et al. Primaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms. Malar J. , v. 16, n. 1, 110, 2017.
dc.identifier1475-2875
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/26554
dc.identifier10.1186/s12936-017-1755-6
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8849628
dc.descriptionBackground: Primaquine is an anti-malarial used to prevent Plasmodium vivax relapses and malaria transmission. However, PQ metabolites cause haemolysis in patients deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Fifteen PQ-thiazolidinone derivatives, synthesized through one-post reactions from primaquine, arenealdehydes and mercaptoacetic acid, were evaluated in parallel in several biological assays, including ability to block malaria transmission to mosquitoes. Results: All primaquine derivatives (PQ-TZs) exhibited lower cell toxicity than primaquine; none caused haemolysis to normal or G6PD-deficient human erythrocytes in vitro. Sera from mice pretreated with the test compounds thus assumed to have drug metabolites, caused no in vitro haemolysis of human erythrocytes, whereas sera from mice pretreated with primaquine did cause haemolysis. The ability of the PQ-TZs to block malaria transmission was evaluated based on the oocyst production and percentage of mosquitoes infected after a blood meal in drug pre-treated animals with experimental malaria caused by either Plasmodium gallinaceum or Plasmodium berghei; four and five PQ-TZs significantly inhibited sporogony in avian and in rodent malaria, respectively. Selected PQ-TZs were tested for their inhibitory activity on P. berghei liver stage development, in mice and in vitro, one compound (4m) caused a 3-day delay in the malaria pre-patent period. Conclusions: The compound 4m was the most promising, blocking malaria transmissions and reducing the number of exoerythrocytic forms of P. berghei (EEFs) in hepatoma cells in vitro and in mice in vivo. The same compound also caused a 3-day delay in the malaria pre-patent period.
dc.description2022-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherBioMed Central
dc.rightsrestricted access
dc.subjectMalaria
dc.subjectTiazolidinonas
dc.subjectEsporogonia
dc.subjectPlasmodium berghei
dc.subjectPlasmodium gallinaceum
dc.subjectBloqueando a transmissão da malária
dc.subjectEstágios exoeritrocíticos
dc.subjectesporozoítos
dc.subjectMalaria
dc.subjectThiazolidinones
dc.subjectSporogony
dc.subjectPlasmodium berghei
dc.subjectPlasmodium gallinaceum
dc.subjectBlocking malaria transmission
dc.subjectExoerythrocytic stages
dc.subjectsporozoites
dc.titlePrimaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms
dc.typeArticle


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