A-Z Index × Submit A-Z Index × Submit A-Z Index Search Dropdown × Submit Facebook Twitter LinkedIn Syndicate Emerging Infectious Disease journal ISSN: 1080-6059 Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.
The empirical discovery of the therapeutic power of Cinchona tree bark in the 17th Century has been one of the most important achievements in the history of medicine in its fight against malaria. Only after 2 centuries, since the isolation of its main alkaloid, quinine, could other important antimalarials, such as chloroquine, be synthesized, all of which helped to save hundreds of millions of lives. In this historical review, we examine the evidence, accessed from early documentary sources, concerning the discovery of Cinchona and its therapeutic value as an antimalarial during the Viceroyalty of Peru.
The genus Cinchona , family Rubiaceae, comprises 23 tree species ( 1 ). Together, they are called quina , 15-meter-high trees native to South America whose bark, branches, and leaves hold an intense bitter taste ( 2 ). Authors such as Espinosa and Cobo have confused the quina trees of the Cinchona genus with the quina-quina tree of the genus Myroxylon ( 3 ).
Cinchona ’s propensity to treat malaria came at an opportune time, when much of the population of southern Europe was experiencing this disease, during the 17th Century. Classified in 1742 by Carl Linnaeus, Cinchona ’s processed bark was known as Peruvian, Jesuits’, countess’, Loja’s, cardinal’s, or Lugo’s powders and also as Peruvian antitertian and bark of fevers ( 1 ).
Cinchona bark was discovered in the 1600s in the Viceroyalty of Peru as a treatment that could be used to treat fevers in general. In 1820, Pierre-Joseph Pelletier and Joseph Bienaimé Caventou managed to isolate 2 alkaloids in the Cinchona bark, to which they attributed the febrifuge and antiparasitic properties of the substance, calling them quinine and cinconine ( 4 ). However, quinine is the main active principle and alkaloid in Cinchona for treating malaria.
Later, in 1889, Charles Louis Alphonse Laveran (winner of the Nobel Prize in Physiology or Medicine in 1907) discovered the Plasmodium parasite, the causative agent of malaria, and in 1897, Ronald Ross discovered the Anopheles mosquito, the vector that transmits Plasmodium . In 1902, Robert Koch implemented massive chemoprophylaxis in New Guinea, emphasizing malaria-control measures, which were effectively used in World War I. Until then, treatment of malaria relied strongly on extracts from the bark of the Cinchona tree for their antimalarial effect. Not until 1944, with the discovery of quinine’s molecular structure, could antimalarial drugs be synthesized on a commercial scale ( 4 – 6 ).
Although the initial discovery of Cinchona ’s antimalarial effect in humans was empirical, the mechanism of action of the molecules responsible for this effect, such as the alkaloids involved in the schizonticidal effect, was subsequently elucidated. The molecules interfere with the parasite’s ability to detoxify by using quinoline. In vitro studies have been fundamental in determining those mechanisms of action. The effect of quinine inhibiting the heme polymerase extracted from P. falciparum trophozoites and the mechanisms of action of specific alkaloids depend on the chemical structures of quinine, quinidine, 9-epiquinine, and 9-epiqu…