History of Antimalarial Agents


Malaria, a disease caused by parasites of the genus Plasmodium, continues to claim hundreds of thousands of lives every year. Infusions of Cinchona bark provided the first effective cure for malaria in the early 1600s and were used widely for centuries. Quinine, isolated from the Cinchona bark in 1820, was to become the first identified antimalarial drug. Attempts to synthesise quinine chemically were unsuccessful but new synthetic antimalarials based on structural elements of quinine were pioneered by German chemists in the early twentieth century. From these compounds, chloroquine was to become one of the most successful antimalarial agents until drug resistance rendered it, and other subsequent antimalarials, ineffective. Several antimalarials have been developed in response to the growing resistance, the most important of which are the plant‐derived artemisinin derivatives, discovered in China in the 1970s. Current antimalarial therapy recommends combinations of drugs over single‐agent therapy to slow drug resistance.

Key Concepts

  • Malaria, a potentially lethal disease, is caused by parasites of the genus Plasmodium.
  • Malarial infection affects hundreds of millions of individuals annually, chiefly within tropical regions of the world.
  • From the seventeenth century, infusions of Cinchona bark were the only effective antimalarial treatment until its active component, quinine, was isolated in 1820.
  • The first synthetic antimalarials originated from German drug discovery programmes in the 1920s and 1930s.
  • The quinoline nucleus found in quinine became an important structural element of many synthetic antimalarials.
  • Resistance to antimalarials continues to be a serious problem and drove much of the drug discovery in the twentieth century.
  • Antimalarial combination therapies have replaced single‐agent monotherapy in order to slow the development of drug resistance.
  • Many antimalarials recommended for treatment today were first developed in China.
  • Two of the most important antimalarials, quinine and artemisinin, are extracted from natural products (plants).
  • Without a suitable vaccine, drugs remain important in treating malaria.

Keywords: antimalarial agents; quinine; Cinchona bark; chloroquine; arteminisinin; antifolates

Figure 1. Timeline showing the introduction of several antimalarial compounds. The chemical structures of select antimalarials are provided directly above or below the date of release. A vaccine that provides total protection against different species of malaria is still years away, so a pipeline of new antimalarials remains the best treatment for malaria. Inset: Quinoline nucleus, building block of several important antimalarials.


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Further Reading

Greenwood D (2008) Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph. Oxford: Oxford University Press.

Rocco F (2003) Quinine and the Quest for a Cure that Changed the World. London: HarperCollins.

Staines HM and Krishna S (2012) Treatment and Prevention of Malaria: Antimalarial Drug Chemistry, Action and Use. Basel: Springer.

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van Schalkwyk, Donelly A.(Apr 2015) History of Antimalarial Agents. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003624.pub3]