Nature Communications (May 2017)
A tetraoxane-based antimalarial drug candidate that overcomes PfK13-C580Y dependent artemisinin resistance
- Paul M. O’Neill,
- Richard K. Amewu,
- Susan A. Charman,
- Sunil Sabbani,
- Nina F. Gnädig,
- Judith Straimer,
- David A. Fidock,
- Emma R. Shore,
- Natalie L. Roberts,
- Michael H.-L. Wong,
- W. David Hong,
- Chandrakala Pidathala,
- Chris Riley,
- Ben Murphy,
- Ghaith Aljayyoussi,
- Francisco Javier Gamo,
- Laura Sanz,
- Janneth Rodrigues,
- Carolina Gonzalez Cortes,
- Esperanza Herreros,
- Iñigo Angulo-Barturén,
- María Belén Jiménez-Díaz,
- Santiago Ferrer Bazaga,
- María Santos Martínez-Martínez,
- Brice Campo,
- Raman Sharma,
- Eileen Ryan,
- David M. Shackleford,
- Simon Campbell,
- Dennis A. Smith,
- Grennady Wirjanata,
- Rintis Noviyanti,
- Ric N. Price,
- Jutta Marfurt,
- Michael J. Palmer,
- Ian M. Copple,
- Amy E. Mercer,
- Andrea Ruecker,
- Michael J. Delves,
- Robert E. Sinden,
- Peter Siegl,
- Jill Davies,
- Rosemary Rochford,
- Clemens H. M. Kocken,
- Anne-Marie Zeeman,
- Gemma L. Nixon,
- Giancarlo A. Biagini,
- Stephen A. Ward
Affiliations
- Paul M. O’Neill
- Department of Chemistry, University of Liverpool
- Richard K. Amewu
- Department of Chemistry, University of Liverpool
- Susan A. Charman
- Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University
- Sunil Sabbani
- Department of Chemistry, University of Liverpool
- Nina F. Gnädig
- Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons
- Judith Straimer
- Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons
- David A. Fidock
- Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons
- Emma R. Shore
- Department of Chemistry, University of Liverpool
- Natalie L. Roberts
- Department of Chemistry, University of Liverpool
- Michael H.-L. Wong
- Department of Chemistry, University of Liverpool
- W. David Hong
- Department of Chemistry, University of Liverpool
- Chandrakala Pidathala
- Department of Chemistry, University of Liverpool
- Chris Riley
- Department of Chemistry, University of Liverpool
- Ben Murphy
- Department of Chemistry, University of Liverpool
- Ghaith Aljayyoussi
- Research Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine
- Francisco Javier Gamo
- Tres Cantos Medicines Development Campus
- Laura Sanz
- Tres Cantos Medicines Development Campus
- Janneth Rodrigues
- Tres Cantos Medicines Development Campus
- Carolina Gonzalez Cortes
- Tres Cantos Medicines Development Campus
- Esperanza Herreros
- Tres Cantos Medicines Development Campus
- Iñigo Angulo-Barturén
- Tres Cantos Medicines Development Campus
- María Belén Jiménez-Díaz
- Tres Cantos Medicines Development Campus
- Santiago Ferrer Bazaga
- Tres Cantos Medicines Development Campus
- María Santos Martínez-Martínez
- Tres Cantos Medicines Development Campus
- Brice Campo
- Medicines for Malaria Venture, ICC
- Raman Sharma
- Research Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine
- Eileen Ryan
- Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University
- David M. Shackleford
- Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University
- Simon Campbell
- Medicines for Malaria Venture, ICC
- Dennis A. Smith
- Medicines for Malaria Venture, ICC
- Grennady Wirjanata
- Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University
- Rintis Noviyanti
- Eijkman Institute for Molecular Biology
- Ric N. Price
- Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University
- Jutta Marfurt
- Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University
- Michael J. Palmer
- Medicines for Malaria Venture, ICC
- Ian M. Copple
- Department of Pharmacology, School of Biomedical Sciences, MRC Centre for Drug Safety Science, University of Liverpool
- Amy E. Mercer
- Department of Pharmacology, School of Biomedical Sciences, MRC Centre for Drug Safety Science, University of Liverpool
- Andrea Ruecker
- Department of Life Sciences, Imperial College London
- Michael J. Delves
- Department of Life Sciences, Imperial College London
- Robert E. Sinden
- Department of Life Sciences, Imperial College London
- Peter Siegl
- Medicines for Malaria Venture, ICC
- Jill Davies
- Research Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine
- Rosemary Rochford
- Department of Immunology and Microbiology, University of Colorado
- Clemens H. M. Kocken
- Department of Parasitology, Biomedical Primate Research Centre
- Anne-Marie Zeeman
- Department of Parasitology, Biomedical Primate Research Centre
- Gemma L. Nixon
- Department of Chemistry, University of Liverpool
- Giancarlo A. Biagini
- Research Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine
- Stephen A. Ward
- Research Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine
- DOI
- https://doi.org/10.1038/ncomms15159
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 10
Abstract
Artemisinin-resistantPlasmodium is an increasing problem. Here, using a medicinal chemistry programme, the authors identify a tetraoxane-based drug candidate that shows no cross-resistance with an artemisinin-resistant strain (PfK13-C580Y) and is efficient in Plasmodiummouse models.