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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/29981
Title: Spiroindolones, a potent compound class for the treatment of malaria
Authors: 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
Francois Nosten
Laurent Renia
Veronique Dartois
Thomas H. Keller
David A. Fidock
Elizabeth A. Winzeler
Thierry T. Diagana
Swiss Tropical and Public Health Institute (Swiss TPH)
Universitat Basel
The Genomics Institute of the Novartis Research Foundation
Novartis Institute for Tropical Diseases Pte. Ltd.
Columbia University Medical Center
Agency for Science, Technology and Research, Singapore
National University of Singapore
Scripps Research Institute
Pennsylvania State University
Novartis International AG
Shoklo Malaria Research Unit
Mahidol University
Nuffield Department of Clinical Medicine
Keywords: Multidisciplinary
Issue Date: 3-Sep-2010
Citation: Science. Vol.329, No.5996 (2010), 1175-1180
Abstract: Recent reports of increased tolerance to artemisinin derivatives - the most recently adopted class of antimalarials - have prompted a need for new treatments. The spirotetrahydro-β-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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77956280420&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/29981
ISSN: 10959203
00368075
Appears in Collections:Scopus 2006-2010

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