Xanthones as antimalarial agents: Discovery, mode of action, and optimization

M. Riscoe, J. X. Kelly, R. Winter

Research output: Contribution to journalReview articlepeer-review

97 Scopus citations


It is believed that at no time in the history of the human race malaria has been absent. This disease, which is cased by protozoa of the genus Plasmodium, in all likelihood has been responsible for the death of about half of all people who ever lived. Even today, after attempts at intervention on a worldwide scale, malaria remains the most significant parasitic disease in the tropics and sub-tropics, where it causes at least 500 million clinical episodes and claims 1.5 million lives each year, mostly young children and pregnant women. Widespread resistance to the best and least expensive antimalarials, chloroquine and S/P (i.e., a combination of sulfadoxine and pyrimethamine), combined with an increasing tolerance to insecticides in the mosquito vector, threaten a global malaria tragedy unless new countermeasures are developed. For malaria therapy, the great panacea would be the development of a long-lasting vaccine, but until this becomes a reality, people living in and traveling to endemic regions must rely on a dwindling cache of more expensive drugs; many beyond the economic reach of impoverished people living in malarious regions of the world. Our course to recognition of xanthones as potential antimalarial agents took a rather circuitous route, involving both serendipity and empiricism, and is described together with mechanistic details of drug action. From a chance encounter with a sea urchin collected near the city of Cannon Beach on the Oregon coast to naturally occurring and functionalized xanthones, it is revealed how these compounds target the Plasmodium parasite's most vulnerable feature - the digestive vacuole.

Original languageEnglish (US)
Pages (from-to)2539-2549
Number of pages11
JournalCurrent Medicinal Chemistry
Issue number21
StatePublished - 2005
Externally publishedYes


  • Chemotherapy
  • Drug
  • Heme
  • Hemozoin
  • Leishmaniasis
  • Malaria
  • Plasmodium falciparum
  • Xanthone

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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