Discovery of dual function acridones as a new antimalarial chemotype

Jane X. Kelly (), Martin J. Smilkstein, Reto Brun, Sergio Wittlin, Roland A. Cooper, Kristin D. Lane, Aaron Janowsky, Robert A. Johnson, Rozalia A. Dodean, Rolf Winter, David J. Hinrichs and Michael K. Riscoe ()
Additional contact information
Jane X. Kelly: Portland Veterans Affairs Medical Centre, Portland, Oregon 97239, USA
Martin J. Smilkstein: Portland Veterans Affairs Medical Centre, Portland, Oregon 97239, USA
Reto Brun: Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland
Sergio Wittlin: Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland
Roland A. Cooper: Old Dominion University, Norfolk, Virginia 23529, USA
Kristin D. Lane: Old Dominion University, Norfolk, Virginia 23529, USA
Aaron Janowsky: Portland Veterans Affairs Medical Centre, Portland, Oregon 97239, USA
Robert A. Johnson: Portland Veterans Affairs Medical Centre, Portland, Oregon 97239, USA
Rozalia A. Dodean: Portland Veterans Affairs Medical Centre, Portland, Oregon 97239, USA
Rolf Winter: Portland Veterans Affairs Medical Centre, Portland, Oregon 97239, USA
David J. Hinrichs: Portland Veterans Affairs Medical Centre, Portland, Oregon 97239, USA
Michael K. Riscoe: Portland Veterans Affairs Medical Centre, Portland, Oregon 97239, USA

Nature, 2009, vol. 459, issue 7244, 270-273

Abstract: New ways with antimalarials The emergence of drug resistance is a continued problem in the battle against malaria. A new class of antimalarial could help to counteract that problem by making possible a novel approach to combination therapy. The dual function acridone compounds combine the haem-targeting antimalarial action of conventional antimalarial acridones with a second active region in the molecule. This boosts the efficacy of established antimalarials such as chloroquine, amodiaquine, quinine and piperaquine synergistically, in some instances overcoming prior resistance to some of these drugs in the Plasmodium falciparum parasites.

Date: 2009
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DOI: 10.1038/nature07937

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