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The anthraquinone emodin inhibits the non-exported FIKK kinase from Plasmodium falciparum

Benjamin C Lin1, Darcy R Harris1, Lucy M D Kirkman1

  • 1Department of Chemistry, Franklin & Marshall College, Lancaster, PA, United States.

Bioorganic Chemistry
|October 9, 2017
PubMed

Insights

Researchers identified emodin as a specific inhibitor for FIKK 8, a Plasmodium falciparum kinase. This discovery is crucial for developing new malaria treatments by targeting unique parasite kinases.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Biochemistry

Background:

  • The FIKK kinase family is unique to Apicomplexan parasites, including malaria parasites.
  • Plasmodium falciparum, the causative agent of severe malaria, possesses 19 FIKK kinases, many exported into host red blood cells.

Purpose of the Study:

  • To confirm FIKK 8 as a non-exported FIKK kinase.
  • To identify inhibitors of Plasmodium falciparum FIKK 8 (PfFk8) for functional studies.

Main Methods:

  • Expression and purification of the recombinant PfFk8 kinase domain.
  • In vitro kinase inhibition assays using emodin and related anthraquinones.

Main Results:

  • Emodin demonstrated significant inhibitory activity against PfFk8 with an IC50 of 2μM.
  • Structural analysis suggests the specific substitution pattern of emodin is key for PfFk8 inhibition.
  • Closely related anthraquinones did not inhibit PfFk8, indicating high specificity.

Conclusions:

  • Emodin is the first identified inhibitor of a Plasmodium falciparum FIKK kinase.
  • This finding provides a foundation for developing targeted inhibitors of FIKK kinases to understand their roles in malaria pathogenesis.
Keywords:
AnthraquinoneEmodinFIKK kinaseKinaseMalariaPlasmodium falciparumSecreted

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