1. Academic Validation
  2. Imidazoquines as antimalarial and antipneumocystis agents

Imidazoquines as antimalarial and antipneumocystis agents

  • J Med Chem. 2009 Dec 10;52(23):7800-7. doi: 10.1021/jm900738c.
Nuno Vale 1 Miguel Prudêncio Catarina A Marques Margaret S Collins Jiri Gut Fátima Nogueira Joana Matos Philip J Rosenthal Melanie T Cushion Virgílio E do Rosário Maria M Mota Rui Moreira Paula Gomes
Affiliations

Affiliation

  • 1 Departamento de Quimica, Faculdade de Ciencias, Centro de Investigacão em Química da Universidade do Porto, Universidade do Porto, Rua do Campo Alegre 687, P-4169-007 Porto, Portugal.
Abstract

Peptidomimetic imidazolidin-4-one derivatives of primaquine (imidazoquines) recently displayed in vitro activity against blood schizonts of a chloroquine-resistant strain of Plasmodium falciparum. Preliminary studies with a subset of such imidazoquines showed them to both block transmission of P. berghei malaria from mouse to mosquito and be highly stable toward hydrolysis at physiological conditions. This prompted us to have deeper insight into the activity of imidazoquines against both Plasmodia and Pneumocystis carinii, on which primaquine is also active. Full assessment of the in vivo transmission-blocking activity of imidazoquines, in vitro tissue-schizontocidal activity on P. berghei-infected hepatocytes, and in vitro anti-P. carinii activity is now reported. All compounds were active in these biological assays, with generally lower activity than the parent drug. However, imidazoquines' stability against both oxidative deamination and proteolytic degradation suggest that they will probably have higher oral bioavailability and lower hematotoxicity than primaquine, which might translate into higher therapeutic indexes.

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