Human p38 mitogen-activated protein kinase inhibitor drugs inhibit Plasmodium falciparum replication

Michael J. Brumlik, Standwell Nkhoma, Mark J. Kious, George R. Thompson, Thomas F Patterson, John J. Siekierka, Tim J C Anderson, Tyler J Curiel

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We recently demonstrated that human p38 mitogen-activated protein kinase (MAPK) inhibitors reduced in vitro and in vivo replication of the protozoan parasites Toxoplasma gondii and Encephalitozoon cuniculi. In this study, we assessed the efficacy of five p38 MAPK inhibitors to block the replication of Plasmodium falciparum in human erythrocytes cultured ex vivo and demonstrate that the pyridinylimidazole RWJ67657 and the pyrrolobenzimidazole RWJ68198 reduced P. falciparum replication, yielded trophozoites that were greatly diminished in size at 24. h, and that these two agents interfered with stage differentiation. Interestingly, the chloroquine-resistant strain W2 was significantly more sensitive to these drugs than was the chloroquine-sensitive strain HB3. These results suggest that pyridinylimidazoles and pyrrolobenzimidazoles designed to inhibit human p38 MAPK activation can be developed to treat malaria.

Original languageEnglish (US)
Pages (from-to)170-175
Number of pages6
JournalExperimental Parasitology
Volume128
Issue number2
DOIs
StatePublished - Jun 2011

Fingerprint

p38 Mitogen-Activated Protein Kinases
Plasmodium falciparum
Protein Kinase Inhibitors
Chloroquine
Encephalitozoon cuniculi
Pharmaceutical Preparations
Trophozoites
Toxoplasma
Malaria
Parasites
Erythrocytes

Keywords

  • Indole-5-carboxamide
  • Mitogen-activated protein kinase
  • Plasmodium falciparum
  • Pyridinylimidazole
  • Pyrrolobenzimidazole

ASJC Scopus subject areas

  • Parasitology
  • Immunology

Cite this

Human p38 mitogen-activated protein kinase inhibitor drugs inhibit Plasmodium falciparum replication. / Brumlik, Michael J.; Nkhoma, Standwell; Kious, Mark J.; Thompson, George R.; Patterson, Thomas F; Siekierka, John J.; Anderson, Tim J C; Curiel, Tyler J.

In: Experimental Parasitology, Vol. 128, No. 2, 06.2011, p. 170-175.

Research output: Contribution to journalArticle

Brumlik, Michael J. ; Nkhoma, Standwell ; Kious, Mark J. ; Thompson, George R. ; Patterson, Thomas F ; Siekierka, John J. ; Anderson, Tim J C ; Curiel, Tyler J. / Human p38 mitogen-activated protein kinase inhibitor drugs inhibit Plasmodium falciparum replication. In: Experimental Parasitology. 2011 ; Vol. 128, No. 2. pp. 170-175.
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