Plasmodium berghei: In vitro and in vivo activity of dequalinium

  • Rodrigues J
  • Gamboa de Domínguez N
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Abstract

Bisquinoline compounds have exhibited remarkable activity in vitro and in vivo against Plasmodium parasites by inhibition of heme detoxification. We have tested the ability of dequalinium 1,1′-(1,10-decanediyl)bis(4-amino-2-methylquinoline), a known antimicrobial agent, to inhibit β-hematin synthesis using a non-emzymatic colorimetric assay and globin proteolysis by electrophoretic analysis (SDS-PAGE-15%). Dequalinium was able to inhibit both processes in vitro with close correlation to a murine malaria model, reducing parasitemia levels, prolonging the survival time post-infection and curing 40% of infected mice using a combination therapy with a loading dose of chloroquine. These results confirm that dequalinium is a promising lead for antimalarial drug development. © 2006 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Bisquinolines
  • CQ
  • DMSO
  • DQ
  • GSH
  • Globin
  • Heme
  • LEP
  • Malaria
  • P. berghei
  • PBS
  • PEP
  • Plasmodium berghei
  • RBC
  • SDS-PAGE
  • chloroquine
  • dequalinium
  • dimethyl sulfoxide
  • glutathione
  • leupeptin
  • pepstatin
  • phosphate-buffered saline
  • red blood cells
  • sodium dodecyl sulfate polyacrylamide gel electrophoresis
  • β-Hematin

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Authors

  • Juan Ricardo Rodrigues

  • Neira Gamboa de Domínguez

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