Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/26554
Type
ArticleCopyright
Restricted access
Embargo date
2022-01-01
Collections
Metadata
Show full item record
PRIMAQUINE-THIAZOLIDINONES BLOCK MALARIA TRANSMISSION AND DEVELOPMENT OF THE LIVER EXOERYTHROCYTIC FORMS
Tiazolidinonas
Esporogonia
Plasmodium berghei
Plasmodium gallinaceum
Bloqueando a transmissão da malária
Estágios exoeritrocíticos
esporozoítos
Thiazolidinones
Sporogony
Plasmodium berghei
Plasmodium gallinaceum
Blocking malaria transmission
Exoerythrocytic stages
sporozoites
Author
Affilliation
Fundação Osvaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, Brazil/Department of Molecular Microbiology and Immunology. Johns Hopkins Bloomberg School of Public Health. Baltimore, MD, USA.
Fundação Osvaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Pelotas. Centro de Ciências Químicas, Farmacêuticas e de Alimentos. Laboratório de Química Aplicada à Bioativos. Pelotas, RS, Brazil.
Fundação Osvaldo Cruz. Laboratório de Epidemiologia. Porto Velho, RO, Brazil.
Universidade Federal de Pelotas. Centro de Ciências Químicas, Farmacêuticas e de Alimentos. Laboratório de Química Aplicada à Bioativos. Pelotas, RS, Brazil.
Universidade Federal de Pelotas. Centro de Ciências Químicas, Farmacêuticas e de Alimentos. Laboratório de Química Aplicada à Bioativos. Pelotas, RS, Brazil
Department of Molecular Microbiology and Immunology. Johns Hopkins Bloomberg School of Public Health. Baltimore, MD, USA.
Department of Molecular Microbiology and Immunology. Johns Hopkins Bloomberg School of Public Health. Baltimore, MD, USA.
Fundação Osvaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, Brazil.
Fundação Osvaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Pelotas. Centro de Ciências Químicas, Farmacêuticas e de Alimentos. Laboratório de Química Aplicada à Bioativos. Pelotas, RS, Brazil.
Fundação Osvaldo Cruz. Laboratório de Epidemiologia. Porto Velho, RO, Brazil.
Universidade Federal de Pelotas. Centro de Ciências Químicas, Farmacêuticas e de Alimentos. Laboratório de Química Aplicada à Bioativos. Pelotas, RS, Brazil.
Universidade Federal de Pelotas. Centro de Ciências Químicas, Farmacêuticas e de Alimentos. Laboratório de Química Aplicada à Bioativos. Pelotas, RS, Brazil
Department of Molecular Microbiology and Immunology. Johns Hopkins Bloomberg School of Public Health. Baltimore, MD, USA.
Department of Molecular Microbiology and Immunology. Johns Hopkins Bloomberg School of Public Health. Baltimore, MD, USA.
Fundação Osvaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, Brazil.
Abstract
Background: 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.
Keywords in Portuguese
MalariaTiazolidinonas
Esporogonia
Plasmodium berghei
Plasmodium gallinaceum
Bloqueando a transmissão da malária
Estágios exoeritrocíticos
esporozoítos
Keywords
MalariaThiazolidinones
Sporogony
Plasmodium berghei
Plasmodium gallinaceum
Blocking malaria transmission
Exoerythrocytic stages
sporozoites
Share