Spiroindolones, a Potent Compound Class for the Treatment of Malaria-Reference-Cited by-同舟云学术

Spiroindolones, a Potent Compound Class for the Treatment of Malaria

Published:2010-09-03 Issue:5996 Volume:329 Page:1175-1180
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Rottmann Matthias¹²,McNamara Case³,Yeung Bryan K. S.⁴,Lee Marcus C. S.⁵,Zou Bin⁴,Russell Bruce⁶⁷,Seitz Patrick¹²,Plouffe David M.³,Dharia Neekesh V.⁸,Tan Jocelyn⁴,Cohen Steven B.³,Spencer Kathryn R.⁸,González-Páez Gonzalo E.⁸,Lakshminarayana Suresh B.⁴,Goh Anne⁴,Suwanarusk Rossarin⁶,Jegla Timothy⁹,Schmitt Esther K.¹⁰,Beck Hans-Peter¹²,Brun Reto¹²,Nosten Francois¹¹¹²¹³,Renia Laurent⁶,Dartois Veronique⁴,Keller Thomas H.⁴,Fidock David A.⁵¹⁴,Winzeler Elizabeth A.³⁸,Diagana Thierry T.⁴

Affiliation:

1. Swiss Tropical and Public Health Institute, Parasite Chemotherapy, CH-4002 Basel, Switzerland.

2. University of Basel, CH-4003 Basel, Switzerland.

3. Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.

4. Novartis Institute for Tropical Diseases, 138670 Singapore.

5. Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.

6. Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648, Singapore.

7. Department of Microbiology, National University of Singapore, 117597, Singapore.

8. Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

9. Department of Biology and Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.

10. Natural Products Unit, Novartis Pharma AG, CH-4002 Basel, Switzerland.

11. Shoklo Malaria Research Unit, Mae Sot, Tak 63110, Thailand.

12. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

13. Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LJ, UK.

14. Department of Medicine (Division of Infectious Diseases), Columbia University Medical Center, New York, NY 10032, USA.

Abstract

Antimalarial Drug Candidate Spiroindolones were discovered as promising antimalarial drug candidates through a high-throughput screening approach that should be applicable to a range of neglected infectious diseases. Rottmann et al. (p. 1175 ; see the Perspective by

Wells

) present the preclinical profile for an optimized spiroindolone drug candidate, NITD609. They obtained evidence for a decrease in drug sensitivity in strains of the malaria parasite Plasmodium falciparum bearing amino acid mutations in the P-type ATPase, indicating possible mechanisms of action and/or resistance.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference42 articles.

1. WHO World Malaria Report 2009; www.who.int/malaria/world_malaria_report_2009/en/

2. Malaria: progress, perils, and prospects for eradication

3. Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria

4. Artemisinin Resistance inPlasmodium falciparumMalaria

5. Evidence of Artemisinin-Resistant Malaria in Western Cambodia

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