Spiroindolones, a potent compound class for the treatment of malaria

Recent reports of increased tolerance to artemisinin derivatives--the most recently adopted class of antimalarials--have prompted a need for new treatments. The spirotetrahydro-beta-carbolines, or spiroindolones, are potent drugs that kill the blood stages of Plasmodium falciparum and Plasmodium vivax clinical isolates at low nanomolar concentration. Spiroindolones rapidly inhibit protein synthesis in P. falciparum, an effect that is ablated in parasites bearing nonsynonymous mutations in the gene encoding the P-type cation-transporter ATPase4 (PfATP4). The optimized spiroindolone NITD609 shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model.

Rottmann, Matthias
McNamara, Case
Yeung, Bryan K. S.
Lee, Marcus C. S.
Zou, Bin
Russell, Bruce
Seitz, Patrick
Plouffe, David M.
Dharia, Neekesh V.
Tan, Jocelyn
Cohen, Steven B.
Spencer, Kathryn R.
González-Páez, Gonzalo E.
Lakshminarayana, Suresh B.
Goh, Anne
Suwanarusk, Rossarin
Jegla, Timothy
Schmitt, Esther K.
Beck, Hans-Peter
Brun, Reto
Nosten, François
Renia, Laurent
Dartois, Veronique
Keller, Thomas H.
Fidock, David A.
Winzeler, Elizabeth A.
Diagana, Thierry T.
Item Type: 
Journal Article
Publication Title: 
Science (New York, N.Y.)
Journal Abbreviation: 
Publication Date: 
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PMID: 20813948 PMCID: PMC3050001

Turabian/Chicago Citation

Matthias Rottmann, Case McNamara, Bryan K. S. Yeung, Marcus C. S. Lee, Bin Zou, Bruce Russell, Patrick Seitz, David M. Plouffe, Neekesh V. Dharia, Jocelyn Tan, Steven B. Cohen, Kathryn R. Spencer, Gonzalo E. González-Páez, Suresh B. Lakshminarayana, Anne Goh, Rossarin Suwanarusk, Timothy Jegla, Esther K. Schmitt, Hans-Peter Beck, Reto Brun, François Nosten, Laurent Renia, Veronique Dartois, Thomas H. Keller, David A. Fidock, Elizabeth A. Winzeler and Thierry T. Diagana. 9/3/2010. "Spiroindolones, a potent compound class for the treatment of malaria." Science (New York, N.Y.) 329: 5996: 1175-1180. 10.1126/science.1193225.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1126/science.1193225 | issn = 1095-9203 | volume = 329 | pages = 1175-1180 | last = Rottmann | first = Matthias | coauthors = McNamara, Case, Yeung, Bryan K. S., Lee, Marcus C. S., Zou, Bin, Russell, Bruce, Seitz, Patrick, Plouffe, David M., Dharia, Neekesh V., Tan, Jocelyn, Cohen, Steven B., Spencer, Kathryn R., González-Páez, Gonzalo E., Lakshminarayana, Suresh B., Goh, Anne, Suwanarusk, Rossarin, Jegla, Timothy, Schmitt, Esther K., Beck, Hans-Peter, Brun, Reto, Nosten, François, Renia, Laurent, Dartois, Veronique, Keller, Thomas H., Fidock, David A., Winzeler, Elizabeth A., Diagana, Thierry T. | title = Spiroindolones, a potent compound class for the treatment of malaria | journal = Science (New York, N.Y.) | date = 9/3/2010 | pmid = | pmc = }} </ref>